Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T59328 | Target Info | |||
| Target Name | Epidermal growth factor receptor (EGFR) | ||||
| Synonyms | Receptor tyrosine-protein kinase erbB-1; Proto-oncogene c-ErbB-1; HER1; ERBB1; ERBB | ||||
| Target Type | Successful Target | ||||
| Gene Name | EGFR | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Gefitinib | Ligand Info | |||
| Canonical SMILES | COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4 | ||||
| InChI | 1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27) | ||||
| InChIKey | XGALLCVXEZPNRQ-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 123631 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3UG2 Crystal structure of the mutated EGFR kinase domain (G719S/T790M) in complex with gefitinib | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [1] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLSSGTVYKG729 LWIPEGEKVK739 IPVAIKESPK754 ANKEILDEAY 764 VMASVDNPHV774 CRLLGICLTS784 TVQLIMQLMP794 FGCLLDYVRE804 HKDNIGSQYL 814 LNWCVQIAKG824 MNYLEDRRLV834 HRDLAARNVL844 VKTPQHVKIT854 DFGLAKLLGA 864 EEKEYHAEGG874 KVPIKWMALE884 SILHRIYTHQ894 SDVWSYGVTV904 WELMTFGSKP 914 YDGIPASEIS924 SILEKGERLP934 QPPICTIDVY944 MIMVKCWMID954 ADSRPKFREL 964 IIEFSKMARD974 PQRYLVIQGD984 ERMHLEDMDD1009 VVDADEYLI
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| PDB ID: 4WKQ 1.85 angstrom structure of EGFR kinase domain with gefitinib | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [2] |
| PDB Sequence |
AMGEAPNQAL
703 LRILKETEFK713 KIKVLGSGTV726 YKGLWIPEGE736 KVKIPVAIKE746 SPKANKEILD 761 EAYVMASVDN771 PHVCRLLGIC781 LTSTVQLITQ791 LMPFGLLDYV802 REHKDNIGSQ 812 YLLNWCVQIA822 KGMNYLEDRR832 LVHRDLAARN842 VLVKTPQHVK852 ITDFGLAKLL 862 GAEEKEYHAE872 GGKVPIKWMA882 LESILHRIYT892 HQSDVWSYGV902 TVWELMTFGS 912 KPYDGIPASE922 ISSILEKGER932 LPQPPICTID942 VYMIMVKCWM952 IDADSRPKFR 962 ELIIEFSKMA972 RDPQRYLVIQ982 GDMDDVVDAD1014 EYLIPQ
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LEU718
3.461
GLY719
4.997
VAL726
4.033
ALA743
3.280
ILE744
4.603
LYS745
3.414
GLU762
3.362
MET766
3.373
LEU788
3.201
ILE789
4.257
THR790
3.378
|
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| PDB ID: 4I22 Structure of the monomeric (V948R)gefitinib/erlotinib resistant double mutant (L858R+T790M) EGFR kinase domain co-crystallized with gefitinib | ||||||
| Method | X-ray diffraction | Resolution | 1.71 Å | Mutation | Yes | [3] |
| PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRK754 ANKEILDEAY 764 VMASVDNPHV774 CRLLGICLTS784 TVQLIMQLMP794 FGCLLDYVRE804 HKDNIGSQYL 814 LNWCVQIAKG824 MNYLEDRRLV834 HRDLAARNVL844 VKTPQHVKIT854 DFGRAKLLVP 877 IKWMALESIL887 HRIYTHQSDV897 WSYGVTVWEL907 MTFGSKPYDG917 IPASEISSIL 927 EKGERLPQPP937 ICTIDVYMIM947 RKCWMIDADS957 RPKFRELIIE967 FSKMARDPQR 977 YLVIQGDERM987 HLPSPTDSNF997 YRALMDEEDM1007 DDVVDAD
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LEU718
3.130
GLY719
3.916
VAL726
3.772
ALA743
3.482
ILE744
3.876
LYS745
3.454
LEU788
3.309
ILE789
4.442
MET790
3.435
GLN791
3.204
|
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| PDB ID: 2ITZ Crystal structure of EGFR kinase domain L858R mutation in complex with Iressa | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLGSGAFGTV726 YKGLWIPEGE736 KVKIPVAIKE746 LREATSPKAN 756 KEILDEAYVM766 ASVDNPHVCR776 LLGICLTSTV786 QLITQLMPFG796 CLLDYVREHK 806 DNIGSQYLLN816 WCVQIAKGMN826 YLEDRRLVHR836 DLAARNVLVK846 TPQHVKITDF 856 GRAKLLGAEV876 PIKWMALESI886 LHRIYTHQSD896 VWSYGVTVWE906 LMTFGSKPYD 916 GIPASEISSI926 LEKGERLPQP936 PICTIDVYMI946 MVKCWMIDAD956 SRPKFRELII 966 EFSKMARDPQ976 RYLVIQGDER986 MHLPMDEEDM1007 DDVVDADEYL1017 IPQ |
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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 .IRE or .IRE2 or .IRE3 or :3IRE;style chemicals stick;color identity;select .A:718 or .A:719 or .A:726 or .A:743 or .A:744 or .A:745 or .A:762 or .A:766 or .A:788 or .A:789 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:795 or .A:796 or .A:797 or .A:800 or .A:844 or .A:854 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.710
GLY719
4.997
VAL726
3.978
ALA743
3.351
ILE744
4.819
LYS745
3.338
GLU762
3.345
MET766
3.499
LEU788
3.767
ILE789
4.557
THR790
3.201
|
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| PDB ID: 2ITO Crystal structure of EGFR kinase domain G719S mutation in complex with Iressa | ||||||
| Method | X-ray diffraction | Resolution | 3.25 Å | Mutation | Yes | [4] |
| PDB Sequence |
GEAPNQALLR
705 ILKETEFKKI715 KVLSSGAFGT725 VYKGLWIPEG735 EKVKIPVAIK745 ELREATSPKA 755 NKEILDEAYV765 MASVDNPHVC775 RLLGICLTST785 VQLITQLMPF795 GCLLDYVREH 805 KDNIGSQYLL815 NWCVQIAKGM825 NYLEDRRLVH835 RDLAARNVLV845 KTPQHVKITD 855 FGLAKLLGAE865 EVPIKWMALE884 SILHRIYTHQ894 SDVWSYGVTV904 WELMTFGSKP 914 YDGIPASEIS924 SILEKGERLP934 QPPICTIDVY944 MIMVKCWMID954 ADSRPKFREL 964 IIEFSKMARD974 PQRYLVIQGD984 ERMHLMDEED1006 MDDVVDADEY1016 LIP |
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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 .IRE or .IRE2 or .IRE3 or :3IRE;style chemicals stick;color identity;select .A:718 or .A:719 or .A:726 or .A:743 or .A:744 or .A:745 or .A:762 or .A:766 or .A:788 or .A:789 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:795 or .A:796 or .A:797 or .A:800 or .A:844 or .A:854 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.905
SER719
3.393
VAL726
4.240
ALA743
3.397
ILE744
4.427
LYS745
3.481
GLU762
3.244
MET766
3.333
LEU788
3.259
ILE789
4.534
THR790
3.337
|
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| PDB ID: 2ITY Crystal structure of EGFR kinase domain in complex with Iressa | ||||||
| Method | X-ray diffraction | Resolution | 3.42 Å | Mutation | No | [4] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLGSGAFGTV726 YKGLWIPEGE736 KVKIPVAIKE746 LREATSPKAN 756 KEILDEAYVM766 ASVDNPHVCR776 LLGICLTSTV786 QLITQLMPFG796 CLLDYVREHK 806 DNIGSQYLLN816 WCVQIAKGMN826 YLEDRRLVHR836 DLAARNVLVK846 TPQHVKITDF 856 GLAKLLGAEV876 PIKWMALESI886 LHRIYTHQSD896 VWSYGVTVWE906 LMTFGSKPYD 916 GIPASEISSI926 LEKGERLPQP936 PICTIDVYMI946 MVKCWMIDAD956 SRPKFRELII 966 EFSKMARDPQ976 RYLVIQGDER986 MHLDEEDMDD1009 VVDADEYLIP1019 |
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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 .IRE or .IRE2 or .IRE3 or :3IRE;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:726 or .A:743 or .A:744 or .A:745 or .A:762 or .A:766 or .A:788 or .A:789 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:795 or .A:796 or .A:797 or .A:800 or .A:844 or .A:854 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
3.398
GLY719
3.607
SER720
3.911
VAL726
3.945
ALA743
3.595
ILE744
4.971
LYS745
3.657
GLU762
3.411
MET766
2.938
LEU788
3.095
ILE789
4.569
THR790
2.888
|
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| References | Top | ||||
|---|---|---|---|---|---|
| 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 | 1.85 angstrom structure of EGFR kinase domain with gefitinib | ||||
| REF 3 | Insights into the aberrant activity of mutant EGFR kinase domain and drug recognition. Structure. 2013 Feb 5;21(2):209-19. | ||||
| REF 4 | Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007 Mar;11(3):217-27. | ||||
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