Target Binding Site Detail
Target General Information | Top | ||||
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Target ID | T16538 | Target Info | |||
Target Name | EGFR T790M mutant (EGFR T790M) | ||||
Synonyms | Receptor tyrosine-protein kinase erbB-1 T790M mutant; Proto-oncogene c-ErbB-1 T790M mutant; HER1 T790M mutant; Epidermal growth factor receptor T790M mutant; ERBB1 T790M mutant; ERBB T790M mutant | ||||
Target Type | Successful Target | ||||
Gene Name | EGFR | ||||
Biochemical Class | Kinase | ||||
UniProt ID |
Ligand General Information | Top | ||||
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Ligand Name | AMP-PNP | Ligand Info | |||
Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(NP(=O)(O)O)O)O)O)N | ||||
InChI | 1S/C10H17N6O12P3/c11-8-5-9(13-2-12-8)16(3-14-5)10-7(18)6(17)4(27-10)1-26-31(24,25)28-30(22,23)15-29(19,20)21/h2-4,6-7,10,17-18H,1H2,(H,24,25)(H2,11,12,13)(H4,15,19,20,21,22,23)/t4-,6-,7-,10-/m1/s1 | ||||
InChIKey | PVKSNHVPLWYQGJ-KQYNXXCUSA-N | ||||
PubChem Compound ID | 33113 |
Drug Binding Sites of Target | Top | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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PDB ID: 3VJN Crystal structure of the mutated EGFR kinase domain (G719S/T790M) in complex with AMPPNP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 2.34 Å | Mutation | Yes | [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLSSGTVYKG729 LWIPEGEKVK739 IPVAIKELEA750 TSPKANKEIL 760 DEAYVMASVD770 NPHVCRLLGI780 CLTSTVQLIM790 QLMPFGCLLD800 YVREHKDNIG 810 SQYLLNWCVQ820 IAKGMNYLED830 RRLVHRDLAA840 RNVLVKTPQH850 VKITDFGLAK 860 LLGAEEKEYH870 AEGGKVPIKW880 MALESILHRI890 YTHQSDVWSY900 GVTVWELMTF 910 GSKPYDGIPA920 SEISSILEKG930 ERLPQPPICT940 IDVYMIMVKC950 WMIDADSRPK 960 FRELIIEFSK970 MARDPQRYLV980 IQGDDMDDVV1011 DADEYLI
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☰Loading data... Dynamically generated for selected residues. Nodes can be dragged or clicked. Label: Selection: Name:
PDB ID: Option 1, search with your selection (all residues are selected by default) in the loaded structures: Option 2, search with PDB ID and chain name: PDB ID: Chain Name: Option 3, search with a PDB file: Foldseek web server. 1. your selection (all residues are selected by default) in the loaded structures to 2 (Optional). Once you see the structure neighbors, you can view the alignment in iCn3D by inputing a list of PDB chain IDs or AlphaFold UniProt IDs below. The PDB chain IDs are the same as the record names such as "1HHO_A". The UniProt ID is the text between "AF-" and "-F1". For example, the UniProt ID for the record name "AF-P69905-F1-model_v4" is "P69905". Chain ID List: BCIF/MMTF ID: PDB ID: Very high (pLDDT > 90) Confident (90 > pLDDT > 70) Low (70 > pLDDT > 50) Very low (pLDDT < 50) AlphaFold Uniprot ID: PAE Map: NCBI Protein Accession: PDB File: Multiple PDB Files: The custom JSON file on residue colors has the following format for proteins("ALA" and "ARG") and nucleotides("G" and "A"): {"ALA":"#C8C8C8", "ARG":"#145AFF", ..., "G":"#008000", "A":"#6080FF", ...} Residue Color File: The custom file for the structure has two columns separated by space or tab: residue number, and score in the range of 0-100. If you click "Apply Custom Color" button, the scores 0, 50 and 100 correspond to the three colors specified below. If you click "Apply Custom Tube", the selected residues will be displayed in a style similar to "B-factor Tube". Custom File: 1. Score to Color: 0: 50: 100: or 2. You can define your own reference numbers in a custom file using Excel, and then export it as a CSV file. An example file is shown below with cells separated by commas. refnum,11,12,,21,22,,10C,11C,20CThe first row defines the reference residue numbers, which could be any strings. The 1st cell could be anything. The rest cells are reference residue numbers (e.g., 11, 21, 10C, etc.) or empty cells. Each chain has a separate row. The first cell of the second row is the chain ID "1TUP_A". The rest cells are the corresponding real residue numbers for reference residue numbers in the first row. For example, the reference numbers for residues 100, 101, and 132 in the chain 1TUP_A are 11, 12, and 22, respectively. The fourth row shows another set of reference numners for the chain "1TUP_C". It could be a chain from a different structure. To select all residues corresponding to the reference numbers, you can simplay replace ":" with "%" in the Specification. For example, "%12" selects the residue 101 in 1TUP_A and the residue 111 in 1TUP_B. ".A%12" has the chain "A" filter and selects the residue 101 in 1TUP_A. Custom File: ID1: ID2: VAST+ based on VAST: VAST+ based on TM-align: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: The sequence alignment (followed by structure alignment) is based on residue numbers in the First/Master chain: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Option 1: Option 2: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Please specify the mutations with a comma separated mutation list. Each mutation can be specified as "[uppercase PDB ID or AlphaFold UniProt ID]_[Chain Name]_[Residue Number]_[One Letter Mutant Residue]". E.g., the mutation of N501Y in the E chain of PDB 6M0J can be specified as "6M0J_E_501_Y". For AlphaFold structures, the "Chain ID" is "A". If you load a custom structure without PDB or UniProt ID, you can open "Seq. & Annotations" window and find the chain ID such as "stru_A". The part before the underscore is the structure ID, which can be used to specify the mutation such as "stru_A_...". Remember to choose "Show Mutation in: Current Page". Mutations: ID Type: PDB IDAlphaFold UniProt ID Show Mutation in: Current PageNew Page Mol2 File: SDF File: XYZ File: URL in the same host: Multiple mmCIF Files: mmCIF ID: Note: The "biological unit" is the biochemically active form of a biomolecule, or Note: The "biological unit" is the biochemically active form of a biomolecule, BLAST search with the protein sequence ID or FASTA sequence as input. If the protein accession is not a PDB chain, the corresponding AlphaFold UniProt structure is used. Enter a protein sequence ID (or FASTA sequence) and the aligned protein accession, which can be found using the Protein Sequence ID(NCBI protein accession of a sequence): or FASTA sequence: Aligned Protein Accession (or a chain of a PDB): ESM Metagenomic Atlas. The sequence should be less than 400 characters. For any sequence longer than 400, please see the discussion here. The sequence to structure prediction is done via FASTA sequence: Protein/Gene name: PubChem CID/Name/InchI: Chemical SMILES: Share Link URL: Collection File: Structures: 2fofc contour at default threshold or at: σ fofc contour at default threshold or at: σ 2fofc contour at default threshold or at: σ URL in the same host: fofc contour at default threshold or at: σ URL in the same host: Custom Color: Grid Size: Salt Concentration: M Potential contour at: kT/e(25.6mV at 298K) Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Grid Size: Salt Concentration: M Surface with max potential at: kT/e(25.6mV at 298K) Surface: Opacity: Wireframe: Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Potential contour at: kT/e(25.6mV at 298K) Note: Always load a PDB file before loading a PQR or DelPhi potential file. Potential contour at: kT/e(25.6mV at 298K) Grid Size: Salt Concentration: M PQR URL in the same host: Phi URL in the same host: Cube URL in the same host: Note: Always load a PDB file before loading a PQR or DelPhi potential file. Symmetry: Distance: Contact Type:
4. Sort Interactions on: to show two lines of residue nodes to show map with atom details to show interactions with strength parameters in 0-200:
(Note: you can also adjust thresholds at #1 to add/remove interactions.) 5. and select new sets 1. Select sets below or use your current selection: 2. 1. Select sets below or use your current selection. 2. 1. Select sets below or use your current selection: 2. Overall maximum RMSD: Å 3. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. Hold Ctrl key to select multiple nodes/lines. Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Note: Nodes/Residues can be dragged. Both nodes and dashed lines/interactions can be clicked to select residues. Color legend for interactions (dashed lines): Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Hold Ctrl key to select multiple nodes. Scale:
Contour at: σ Contour at: σ Contour at: % of maximum EM values 1. Select the first set: 2. Sphere with a radius: Å 3. Select the second set to apply the sphere: 4. the sphere around the first set of atoms interacting/contacting residue pairs in a file 1. Extracellular membrane Z-axis position: Å 2. intracellular membrane Z-axis position: Å 3. the adjusted membranes 1. Z-axis position of the first X-Y plane: Å 2. Z-axis position of the second X-Y plane: Å 3. the region between the planes to Defined Sets 2. Size: 3. Color: 4. Pick TWO atoms while holding "Alt" key 5. 2. Size: 3. Color: 4. 1. Pick TWO atoms while holding "Alt" key 2. Line Color: 3. 1. Pick TWO atoms while holding "Alt" key 2. Color: 3. 1. Select two sets
3. 1. Select two sets
2. Line style: 3. Line radius: 4. Color: 5. Opacity: 6. 1. Select a set: 2. Shape: 3. Radius: 4. Color: 5. Opacity: 6. 1. Select sets for pairwise distances
Note: Each set is represented by a vector, which is the X-axis of the principle axes. The angles between the vectors are then calculated. 1. Select sets for pairwise angles
1. Pick TWO atoms while holding "Alt" key 2. Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 1. Shininess: (for the shininess of the 3D objects, default 40) 2. Three directional lights: Key Light: (for the light strength of the key light, default 0.8) Fill Light: (for the light strength of the fill light, default 0.4) Back Light: (for the light strength of the back light, default 0.2) 3. Thickness: Line Radius: (for stabilizers, hydrogen bonds, distance lines, default 0.1) Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 4. Show Glycan Cartoon: (0: hide, 1: show, default 0) 5. Show Membrane: (0: hide, 1: show, default 1) 6. Enlarge Command Window: (0: Regular, 1: Large, default 0) 1. URLs Used in Browsers Please copy one of the URLs below. They show the same result. (To add a title to share link, click "Windows > Your Note" and click "File > Share Link" again.) Original URL with commands: Lifelong Short URL:(To replace this URL, send a pull request to update share.html at iCn3D GitHub) Lifelong Short URL + Window Title:(To update the window title, click "Analysis > Your Note/Window Title".) 2. Commands Used in Jupyter Noteboook Please copy the following commands into a cell in Jupyter Notebook to show the same result. More details are at https://github.com/ncbi/icn3d/tree/master/jupyternotebook. Annotations:
Zoom: mouse wheel; Move: left button; Select Multiple Nodes: Ctrl Key and drag an Area Force on Nodes: Label Size: Internal Edges: Color each residue based on the percentage of solvent accessilbe surface area. The color ranges from blue, to white, to red for a percentage of 0, 35(variable), and 100, respectively. Middle Percentage(White): % Select residue based on the percentage of solvent accessilbe surface area. The values are in the range of 0-100. Min Percentage: % Max Percentage: % Select residue based on B-factor/pLDDT. The values are in the range of 0-100. Min B-factor/pLDDT: % Max B-factor/pLDDT: % X: Y: Z: Vector 2, X: Y: Z: The angle is: degree. 1: 5: 9: 13: 2: 6: 10: 14: 3: 7: 11: 15: Choose an Ig template for selected residues: Choose an Ig template to align with selected residues: |
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PDB ID: 7JXQ EGFR kinase (T790M/V948R) in complex with allosteric inhibitor JBJ-09-063 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 1.83 Å | Mutation | Yes | [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLLGAEVPIK879 WMALESILHR889 IYTHQSDVWS899 YGVTVWELMT909 FGSKPYDGIP 919 ASEISSILEK929 GERLPQPPIC939 TIDVYMIMRK949 CWMIDADSRP959 KFRELIIEFS 969 KMARDPQRYL979 VIQGDERMHL989 PSPTDSNFYR999 ALMDEEDM
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☰Loading data... Dynamically generated for selected residues. Nodes can be dragged or clicked. Label: Selection: Name:
PDB ID: Option 1, search with your selection (all residues are selected by default) in the loaded structures: Option 2, search with PDB ID and chain name: PDB ID: Chain Name: Option 3, search with a PDB file: Foldseek web server. 1. your selection (all residues are selected by default) in the loaded structures to 2 (Optional). Once you see the structure neighbors, you can view the alignment in iCn3D by inputing a list of PDB chain IDs or AlphaFold UniProt IDs below. The PDB chain IDs are the same as the record names such as "1HHO_A". The UniProt ID is the text between "AF-" and "-F1". For example, the UniProt ID for the record name "AF-P69905-F1-model_v4" is "P69905". Chain ID List: BCIF/MMTF ID: PDB ID: Very high (pLDDT > 90) Confident (90 > pLDDT > 70) Low (70 > pLDDT > 50) Very low (pLDDT < 50) AlphaFold Uniprot ID: PAE Map: NCBI Protein Accession: PDB File: Multiple PDB Files: The custom JSON file on residue colors has the following format for proteins("ALA" and "ARG") and nucleotides("G" and "A"): {"ALA":"#C8C8C8", "ARG":"#145AFF", ..., "G":"#008000", "A":"#6080FF", ...} Residue Color File: The custom file for the structure has two columns separated by space or tab: residue number, and score in the range of 0-100. If you click "Apply Custom Color" button, the scores 0, 50 and 100 correspond to the three colors specified below. If you click "Apply Custom Tube", the selected residues will be displayed in a style similar to "B-factor Tube". Custom File: 1. Score to Color: 0: 50: 100: or 2. You can define your own reference numbers in a custom file using Excel, and then export it as a CSV file. An example file is shown below with cells separated by commas. refnum,11,12,,21,22,,10C,11C,20CThe first row defines the reference residue numbers, which could be any strings. The 1st cell could be anything. The rest cells are reference residue numbers (e.g., 11, 21, 10C, etc.) or empty cells. Each chain has a separate row. The first cell of the second row is the chain ID "1TUP_A". The rest cells are the corresponding real residue numbers for reference residue numbers in the first row. For example, the reference numbers for residues 100, 101, and 132 in the chain 1TUP_A are 11, 12, and 22, respectively. The fourth row shows another set of reference numners for the chain "1TUP_C". It could be a chain from a different structure. To select all residues corresponding to the reference numbers, you can simplay replace ":" with "%" in the Specification. For example, "%12" selects the residue 101 in 1TUP_A and the residue 111 in 1TUP_B. ".A%12" has the chain "A" filter and selects the residue 101 in 1TUP_A. Custom File: ID1: ID2: VAST+ based on VAST: VAST+ based on TM-align: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: The sequence alignment (followed by structure alignment) is based on residue numbers in the First/Master chain: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Option 1: Option 2: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Please specify the mutations with a comma separated mutation list. Each mutation can be specified as "[uppercase PDB ID or AlphaFold UniProt ID]_[Chain Name]_[Residue Number]_[One Letter Mutant Residue]". E.g., the mutation of N501Y in the E chain of PDB 6M0J can be specified as "6M0J_E_501_Y". For AlphaFold structures, the "Chain ID" is "A". If you load a custom structure without PDB or UniProt ID, you can open "Seq. & Annotations" window and find the chain ID such as "stru_A". The part before the underscore is the structure ID, which can be used to specify the mutation such as "stru_A_...". Remember to choose "Show Mutation in: Current Page". Mutations: ID Type: PDB IDAlphaFold UniProt ID Show Mutation in: Current PageNew Page Mol2 File: SDF File: XYZ File: URL in the same host: Multiple mmCIF Files: mmCIF ID: Note: The "biological unit" is the biochemically active form of a biomolecule, or Note: The "biological unit" is the biochemically active form of a biomolecule, BLAST search with the protein sequence ID or FASTA sequence as input. If the protein accession is not a PDB chain, the corresponding AlphaFold UniProt structure is used. Enter a protein sequence ID (or FASTA sequence) and the aligned protein accession, which can be found using the Protein Sequence ID(NCBI protein accession of a sequence): or FASTA sequence: Aligned Protein Accession (or a chain of a PDB): ESM Metagenomic Atlas. The sequence should be less than 400 characters. For any sequence longer than 400, please see the discussion here. The sequence to structure prediction is done via FASTA sequence: Protein/Gene name: PubChem CID/Name/InchI: Chemical SMILES: Share Link URL: Collection File: Structures: 2fofc contour at default threshold or at: σ fofc contour at default threshold or at: σ 2fofc contour at default threshold or at: σ URL in the same host: fofc contour at default threshold or at: σ URL in the same host: Custom Color: Grid Size: Salt Concentration: M Potential contour at: kT/e(25.6mV at 298K) Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Grid Size: Salt Concentration: M Surface with max potential at: kT/e(25.6mV at 298K) Surface: Opacity: Wireframe: Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Potential contour at: kT/e(25.6mV at 298K) Note: Always load a PDB file before loading a PQR or DelPhi potential file. Potential contour at: kT/e(25.6mV at 298K) Grid Size: Salt Concentration: M PQR URL in the same host: Phi URL in the same host: Cube URL in the same host: Note: Always load a PDB file before loading a PQR or DelPhi potential file. Symmetry: Distance: Contact Type:
4. Sort Interactions on: to show two lines of residue nodes to show map with atom details to show interactions with strength parameters in 0-200:
(Note: you can also adjust thresholds at #1 to add/remove interactions.) 5. and select new sets 1. Select sets below or use your current selection: 2. 1. Select sets below or use your current selection. 2. 1. Select sets below or use your current selection: 2. Overall maximum RMSD: Å 3. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. Hold Ctrl key to select multiple nodes/lines. Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Note: Nodes/Residues can be dragged. Both nodes and dashed lines/interactions can be clicked to select residues. Color legend for interactions (dashed lines): Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Hold Ctrl key to select multiple nodes. Scale:
Contour at: σ Contour at: σ Contour at: % of maximum EM values 1. Select the first set: 2. Sphere with a radius: Å 3. Select the second set to apply the sphere: 4. the sphere around the first set of atoms interacting/contacting residue pairs in a file 1. Extracellular membrane Z-axis position: Å 2. intracellular membrane Z-axis position: Å 3. the adjusted membranes 1. Z-axis position of the first X-Y plane: Å 2. Z-axis position of the second X-Y plane: Å 3. the region between the planes to Defined Sets 2. Size: 3. Color: 4. Pick TWO atoms while holding "Alt" key 5. 2. Size: 3. Color: 4. 1. Pick TWO atoms while holding "Alt" key 2. Line Color: 3. 1. Pick TWO atoms while holding "Alt" key 2. Color: 3. 1. Select two sets
3. 1. Select two sets
2. Line style: 3. Line radius: 4. Color: 5. Opacity: 6. 1. Select a set: 2. Shape: 3. Radius: 4. Color: 5. Opacity: 6. 1. Select sets for pairwise distances
Note: Each set is represented by a vector, which is the X-axis of the principle axes. The angles between the vectors are then calculated. 1. Select sets for pairwise angles
1. Pick TWO atoms while holding "Alt" key 2. Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 1. Shininess: (for the shininess of the 3D objects, default 40) 2. Three directional lights: Key Light: (for the light strength of the key light, default 0.8) Fill Light: (for the light strength of the fill light, default 0.4) Back Light: (for the light strength of the back light, default 0.2) 3. Thickness: Line Radius: (for stabilizers, hydrogen bonds, distance lines, default 0.1) Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 4. Show Glycan Cartoon: (0: hide, 1: show, default 0) 5. Show Membrane: (0: hide, 1: show, default 1) 6. Enlarge Command Window: (0: Regular, 1: Large, default 0) 1. URLs Used in Browsers Please copy one of the URLs below. They show the same result. (To add a title to share link, click "Windows > Your Note" and click "File > Share Link" again.) Original URL with commands: Lifelong Short URL:(To replace this URL, send a pull request to update share.html at iCn3D GitHub) Lifelong Short URL + Window Title:(To update the window title, click "Analysis > Your Note/Window Title".) 2. Commands Used in Jupyter Noteboook Please copy the following commands into a cell in Jupyter Notebook to show the same result. More details are at https://github.com/ncbi/icn3d/tree/master/jupyternotebook. Annotations:
Zoom: mouse wheel; Move: left button; Select Multiple Nodes: Ctrl Key and drag an Area Force on Nodes: Label Size: Internal Edges: Color each residue based on the percentage of solvent accessilbe surface area. The color ranges from blue, to white, to red for a percentage of 0, 35(variable), and 100, respectively. Middle Percentage(White): % Select residue based on the percentage of solvent accessilbe surface area. The values are in the range of 0-100. Min Percentage: % Max Percentage: % Select residue based on B-factor/pLDDT. The values are in the range of 0-100. Min B-factor/pLDDT: % Max B-factor/pLDDT: % X: Y: Z: Vector 2, X: Y: Z: The angle is: degree. 1: 5: 9: 13: 2: 6: 10: 14: 3: 7: 11: 15: Choose an Ig template for selected residues: Choose an Ig template to align with selected residues: |
LEU718
3.794
GLY719
3.569
SER720
3.529
GLY721
3.020
ALA722
3.124
PHE723
4.621
GLY724
3.935
VAL726
3.401
ALA743
3.484
LYS745
2.711
MET790
3.409
|
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PDB ID: 5X2A Crystal structure of EGFR 696-1022 T790M/V948R in complex with SKLB(3) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | Yes | [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLLVPIKWMA882 LESILHRIYT892 HQSDVWSYGV902 TVWELMTFGS912 KPYDGIPASE 922 ISSILEKGER932 LPQPPICTID942 VYMIMRKCWM952 IDADSRPKFR962 ELIIEFSKMA 972 RDPQRYLVIQ982 GDERMHLPSP992 TDSNFYRALM1002 DEEDMVV
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☰Loading data... Dynamically generated for selected residues. Nodes can be dragged or clicked. Label: Selection: Name:
PDB ID: Option 1, search with your selection (all residues are selected by default) in the loaded structures: Option 2, search with PDB ID and chain name: PDB ID: Chain Name: Option 3, search with a PDB file: Foldseek web server. 1. your selection (all residues are selected by default) in the loaded structures to 2 (Optional). Once you see the structure neighbors, you can view the alignment in iCn3D by inputing a list of PDB chain IDs or AlphaFold UniProt IDs below. The PDB chain IDs are the same as the record names such as "1HHO_A". The UniProt ID is the text between "AF-" and "-F1". For example, the UniProt ID for the record name "AF-P69905-F1-model_v4" is "P69905". Chain ID List: BCIF/MMTF ID: PDB ID: Very high (pLDDT > 90) Confident (90 > pLDDT > 70) Low (70 > pLDDT > 50) Very low (pLDDT < 50) AlphaFold Uniprot ID: PAE Map: NCBI Protein Accession: PDB File: Multiple PDB Files: The custom JSON file on residue colors has the following format for proteins("ALA" and "ARG") and nucleotides("G" and "A"): {"ALA":"#C8C8C8", "ARG":"#145AFF", ..., "G":"#008000", "A":"#6080FF", ...} Residue Color File: The custom file for the structure has two columns separated by space or tab: residue number, and score in the range of 0-100. If you click "Apply Custom Color" button, the scores 0, 50 and 100 correspond to the three colors specified below. If you click "Apply Custom Tube", the selected residues will be displayed in a style similar to "B-factor Tube". Custom File: 1. Score to Color: 0: 50: 100: or 2. You can define your own reference numbers in a custom file using Excel, and then export it as a CSV file. An example file is shown below with cells separated by commas. refnum,11,12,,21,22,,10C,11C,20CThe first row defines the reference residue numbers, which could be any strings. The 1st cell could be anything. The rest cells are reference residue numbers (e.g., 11, 21, 10C, etc.) or empty cells. Each chain has a separate row. The first cell of the second row is the chain ID "1TUP_A". The rest cells are the corresponding real residue numbers for reference residue numbers in the first row. For example, the reference numbers for residues 100, 101, and 132 in the chain 1TUP_A are 11, 12, and 22, respectively. The fourth row shows another set of reference numners for the chain "1TUP_C". It could be a chain from a different structure. To select all residues corresponding to the reference numbers, you can simplay replace ":" with "%" in the Specification. For example, "%12" selects the residue 101 in 1TUP_A and the residue 111 in 1TUP_B. ".A%12" has the chain "A" filter and selects the residue 101 in 1TUP_A. Custom File: ID1: ID2: VAST+ based on VAST: VAST+ based on TM-align: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: The sequence alignment (followed by structure alignment) is based on residue numbers in the First/Master chain: (Note: To align chains in custom PDB files, you could load them in "File > Open File > PDB Files (appendable)" and click "Analysis > Defined Sets". Finally select multiple chains in Defined Sets and click "File > Realign Selection".) All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Option 1: Option 2: All chains will be aligned to the first chain in the comma-separated chain IDs. Each chain ID has the form of PDBID_chain (e.g., 1HHO_A, case sensitive) or UniprotID (e.g., P69905 for AlphaFold structures). Chain IDs: Each alignment is defined as " | "-separated residue lists in one line. "10-50" means a range of residues from 10 to 50. Please specify the mutations with a comma separated mutation list. Each mutation can be specified as "[uppercase PDB ID or AlphaFold UniProt ID]_[Chain Name]_[Residue Number]_[One Letter Mutant Residue]". E.g., the mutation of N501Y in the E chain of PDB 6M0J can be specified as "6M0J_E_501_Y". For AlphaFold structures, the "Chain ID" is "A". If you load a custom structure without PDB or UniProt ID, you can open "Seq. & Annotations" window and find the chain ID such as "stru_A". The part before the underscore is the structure ID, which can be used to specify the mutation such as "stru_A_...". Remember to choose "Show Mutation in: Current Page". Mutations: ID Type: PDB IDAlphaFold UniProt ID Show Mutation in: Current PageNew Page Mol2 File: SDF File: XYZ File: URL in the same host: Multiple mmCIF Files: mmCIF ID: Note: The "biological unit" is the biochemically active form of a biomolecule, or Note: The "biological unit" is the biochemically active form of a biomolecule, BLAST search with the protein sequence ID or FASTA sequence as input. If the protein accession is not a PDB chain, the corresponding AlphaFold UniProt structure is used. Enter a protein sequence ID (or FASTA sequence) and the aligned protein accession, which can be found using the Protein Sequence ID(NCBI protein accession of a sequence): or FASTA sequence: Aligned Protein Accession (or a chain of a PDB): ESM Metagenomic Atlas. The sequence should be less than 400 characters. For any sequence longer than 400, please see the discussion here. The sequence to structure prediction is done via FASTA sequence: Protein/Gene name: PubChem CID/Name/InchI: Chemical SMILES: Share Link URL: Collection File: Structures: 2fofc contour at default threshold or at: σ fofc contour at default threshold or at: σ 2fofc contour at default threshold or at: σ URL in the same host: fofc contour at default threshold or at: σ URL in the same host: Custom Color: Grid Size: Salt Concentration: M Potential contour at: kT/e(25.6mV at 298K) Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Grid Size: Salt Concentration: M Surface with max potential at: kT/e(25.6mV at 298K) Surface: Opacity: Wireframe: Note: Only the selected residues are used for DelPhi potential calculation by solving linear Poisson-Boltzmann equation. Potential contour at: kT/e(25.6mV at 298K) Note: Always load a PDB file before loading a PQR or DelPhi potential file. Potential contour at: kT/e(25.6mV at 298K) Grid Size: Salt Concentration: M PQR URL in the same host: Phi URL in the same host: Cube URL in the same host: Note: Always load a PDB file before loading a PQR or DelPhi potential file. Symmetry: Distance: Contact Type:
4. Sort Interactions on: to show two lines of residue nodes to show map with atom details to show interactions with strength parameters in 0-200:
(Note: you can also adjust thresholds at #1 to add/remove interactions.) 5. and select new sets 1. Select sets below or use your current selection: 2. 1. Select sets below or use your current selection. 2. 1. Select sets below or use your current selection: 2. Overall maximum RMSD: Å 3. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. 1. Select sets below: 2. Hold Ctrl key to select multiple nodes/lines. Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Note: Nodes/Residues can be dragged. Both nodes and dashed lines/interactions can be clicked to select residues. Color legend for interactions (dashed lines): Green: H-Bonds; Cyan: Salt Bridge/Ionic; Grey: Contacts Magenta: Halogen Bonds; Red: π-Cation; Blue: π-Stacking Scale: Hold Ctrl key to select multiple nodes. Scale: Hold Ctrl key to select multiple nodes. Scale:
Contour at: σ Contour at: σ Contour at: % of maximum EM values 1. Select the first set: 2. Sphere with a radius: Å 3. Select the second set to apply the sphere: 4. the sphere around the first set of atoms interacting/contacting residue pairs in a file 1. Extracellular membrane Z-axis position: Å 2. intracellular membrane Z-axis position: Å 3. the adjusted membranes 1. Z-axis position of the first X-Y plane: Å 2. Z-axis position of the second X-Y plane: Å 3. the region between the planes to Defined Sets 2. Size: 3. Color: 4. Pick TWO atoms while holding "Alt" key 5. 2. Size: 3. Color: 4. 1. Pick TWO atoms while holding "Alt" key 2. Line Color: 3. 1. Pick TWO atoms while holding "Alt" key 2. Color: 3. 1. Select two sets
3. 1. Select two sets
2. Line style: 3. Line radius: 4. Color: 5. Opacity: 6. 1. Select a set: 2. Shape: 3. Radius: 4. Color: 5. Opacity: 6. 1. Select sets for pairwise distances
Note: Each set is represented by a vector, which is the X-axis of the principle axes. The angles between the vectors are then calculated. 1. Select sets for pairwise angles
1. Pick TWO atoms while holding "Alt" key 2. Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 1. Shininess: (for the shininess of the 3D objects, default 40) 2. Three directional lights: Key Light: (for the light strength of the key light, default 0.8) Fill Light: (for the light strength of the fill light, default 0.4) Back Light: (for the light strength of the back light, default 0.2) 3. Thickness: Line Radius: (for stabilizers, hydrogen bonds, distance lines, default 0.1) Coil Radius: (for coils, default 0.3) Stick Radius: (for sticks, default 0.4) Cross-Linkage Radius: (for cross-linkages, default 0.4) Trace Radius: (for C alpha trace, O3' trace, default 0.4) Ribbon Thickness: (for helix and sheet ribbons, nucleotide ribbons, default 0.2) Protein Ribbon Width: (for helix and sheet ribbons, default 1.3) Nucleotide Ribbon Width: (for nucleotide ribbons, default 0.8) Ball Scale: (for styles 'Ball and Stick' and 'Dot', default 0.3) 4. Show Glycan Cartoon: (0: hide, 1: show, default 0) 5. Show Membrane: (0: hide, 1: show, default 1) 6. Enlarge Command Window: (0: Regular, 1: Large, default 0) 1. URLs Used in Browsers Please copy one of the URLs below. They show the same result. (To add a title to share link, click "Windows > Your Note" and click "File > Share Link" again.) Original URL with commands: Lifelong Short URL:(To replace this URL, send a pull request to update share.html at iCn3D GitHub) Lifelong Short URL + Window Title:(To update the window title, click "Analysis > Your Note/Window Title".) 2. Commands Used in Jupyter Noteboook Please copy the following commands into a cell in Jupyter Notebook to show the same result. More details are at https://github.com/ncbi/icn3d/tree/master/jupyternotebook. Annotations:
Zoom: mouse wheel; Move: left button; Select Multiple Nodes: Ctrl Key and drag an Area Force on Nodes: Label Size: Internal Edges: Color each residue based on the percentage of solvent accessilbe surface area. The color ranges from blue, to white, to red for a percentage of 0, 35(variable), and 100, respectively. Middle Percentage(White): % Select residue based on the percentage of solvent accessilbe surface area. The values are in the range of 0-100. Min Percentage: % Max Percentage: % Select residue based on B-factor/pLDDT. The values are in the range of 0-100. Min B-factor/pLDDT: % Max B-factor/pLDDT: % X: Y: Z: Vector 2, X: Y: Z: The angle is: degree. 1: 5: 9: 13: 2: 6: 10: 14: 3: 7: 11: 15: Choose an Ig template for selected residues: Choose an Ig template to align with selected residues: |
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PDB ID: 4ZSE Crystal structure of EGFR 696-1022 T790M/V948R, crystal form II | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | Yes | [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
PNQALLRILK
708 ETEFKKIKVL718 GSGAFGTVYK728 GLWIPEGEKV738 KIPVAIKELR748 EATSPKANKE 758 ILDEAYVMAS768 VDNPHVCRLL778 GICLTSTVQL788 IMQLMPFGCL798 LDYVREHKDN 808 IGSQYLLNWC818 VQIAKGMNYL828 EDRRLVHRDL838 AARNVLVKTP848 QHVKITDFGL 858 AKLLKVPIKW880 MALESILHRI890 YTHQSDVWSY900 GVTVWELMTF910 GSKPYDGIPA 920 SEISSILEKG930 ERLPQPPICT940 IDVYMIMRKC950 WMIDADSRPK960 FRELIIEFSK 970 MARDPQRYLV980 IQGDERMHLP990 SPTDSNFYRA1000 LMDEEDM
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.497
GLY719
3.647
SER720
3.653
GLY721
3.159
ALA722
3.111
PHE723
4.221
GLY724
3.433
THR725
4.902
VAL726
3.330
ALA743
3.529
LYS745
2.912
MET790
3.937
|
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PDB ID: 7JXP EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-04-125-02 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 2.16 Å | Mutation | Yes | [5] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLVPIKWMAL883 ESILHRIYTH893 QSDVWSYGVT903 VWELMTFGSK913 PYDGIPASEI 923 SSILEKGERL933 PQPPICTIDV943 YMIMRKCWMI953 DADSRPKFRE963 LIIEFSKMAR 973 DPQRYLVIQG983 DERMHLPSPT993 DSNFYRALMD1003 EEDM
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:725 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.704
GLY719
3.437
SER720
3.631
GLY721
3.208
ALA722
2.714
PHE723
4.762
GLY724
3.673
THR725
4.804
VAL726
3.158
ALA743
3.561
LYS745
3.178
MET790
3.439
|
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PDB ID: 7JXM EGFR kinase (T790M/V948R) in complex with osimertinib and EAI045 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | Yes | [5] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLV 876 PIKWMALESI886 LHRIYTHQSD896 VWSYGVTVWE906 LMTFGSKPYD916 GIPASEISSI 926 LEKGERLPQP936 PICTIDVYMI946 MRKCWMIDAD956 SRPKFRELII966 EFSKMARDPQ 976 RYLVIQGDER986 MHLPSPTDSN996 FYRALMDEED1006 M
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.779
GLY719
3.693
SER720
3.456
GLY721
3.061
ALA722
2.985
PHE723
4.900
GLY724
3.498
VAL726
3.350
ALA743
3.545
LYS745
3.365
MET790
3.280
|
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PDB ID: 7LTX EGFR (T790M/V948R) in complex with quinazolinone allosteric inhibitor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [6] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 VPIKWMALES885 ILHRIYTHQS895 DVWSYGVTVW905 ELMTFGSKPY915 DGIPASEISS 925 ILEKGERLPQ935 PPICTIDVYM945 IMRKCWMIDA955 DSRPKFRELI965 IEFSKMARDP 975 QRYLVIQGDE985 RMHLPSPTDS995 NFYRALMDEE1005 DM
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.798
GLY719
3.698
SER720
3.575
GLY721
3.285
ALA722
3.200
PHE723
4.488
GLY724
3.600
THR725
4.882
VAL726
3.400
ALA743
3.488
LYS745
2.828
MET790
3.503
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PDB ID: 7JXK EGFR kinase (T790M/V948R) in complex with PF-06747775 and JBJ-04-125-02 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [5] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLVPIKWMAL883 ESILHRIYTH893 QSDVWSYGVT903 VWELMTFGSK913 PYDGIPASEI 923 SSILEKGERL933 PQPPICTIDV943 YMIMRKCWMI953 DADSRPKFRE963 LIIEFSKMAR 973 DPQRYLVIQG983 DERMHLPSPT993 DSNFYRALMD1003 EEDM
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU718
4.034
GLY719
3.380
SER720
3.454
GLY721
3.210
ALA722
4.122
PHE723
3.571
GLY724
3.313
VAL726
3.145
ALA743
3.272
LYS745
3.100
MET790
3.787
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PDB ID: 6WAK A crystal structure of EGFR(T790M/V948R) in complex with LN3754 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [7] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB Sequence |
QALLRILKET
710 EFKKIKVLGS720 GAFGTVYKGL730 WIPEGEKVKI740 PVAIKELREA750 KANKEILDEA 763 YVMASVDNPH773 VCRLLGICLT783 STVQLIMQLM793 PFGCLLDYVR803 EHKDNIGSQY 813 LLNWCVQIAK823 GMNYLEDRRL833 VHRDLAARNV843 LVKTPQHVKI853 TDFGLAKLVP 877 IKWMALESIL887 HRIYTHQSDV897 WSYGVTVWEL907 MTFGSKPYDG917 IPASEISSIL 927 EKGERLPQPP937 ICTIDVYMIM947 RKCWMIDADS957 RPKFRELIIE967 FSKMARDPQR 977 YLVIQGDERM987 HLPSPTDSNF997 YRALMDEEDM1007 DDVVDAD
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:725 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:854 or .D:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU718
3.460
GLY719
3.570
SER720
3.593
GLY721
3.432
ALA722
3.176
PHE723
3.581
GLY724
3.658
THR725
4.870
VAL726
3.387
ALA743
3.365
LYS745
2.817
MET790
3.950
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References | Top | ||||
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REF 1 | Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor. Oncogene. 2013 Jan 3;32(1):27-38. | ||||
REF 2 | An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer. Nat Cancer. 2022 Apr;3(4):402-417. | ||||
REF 3 | Structural insights into drug development strategy targeting EGFR T790M/C797S. Oncotarget. 2018 Jan 10;9(17):13652-13665. | ||||
REF 4 | Ibrutinib Selectively and Irreversibly Targets EGFR-mutant non-Small Cell Lung Cancer Cells | ||||
REF 5 | Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. doi:10.1038/s41467-022-30258-y. | ||||
REF 6 | Quinazolinones as allosteric fourth-generation EGFR inhibitors for the treatment of NSCLC. Bioorg Med Chem Lett. 2022 Jul 15;68:128718. | ||||
REF 7 | Design of a "Two-in-One" Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites. J Med Chem. 2022 Jan 27;65(2):1370-1383. |
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