Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T94033 | Target Info | |||
| Target Name | Coagulation factor IIa (F2) | ||||
| Synonyms | Prothrombin; Coagulation factor II | ||||
| Target Type | Successful Target | ||||
| Gene Name | F2 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Benzamidine | Ligand Info | |||
| Canonical SMILES | C1=CC=C(C=C1)C(=N)N | ||||
| InChI | 1S/C7H8N2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H3,8,9) | ||||
| InChIKey | PXXJHWLDUBFPOL-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 2332 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3D49 Thrombin Inhibition | ||||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [1] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKEGQPS153 VLQVVNLPIV 163 ERPVCKDSTR173 IRITDNMFCA183 GYKPDEGKRG188 DACEGDSGGP198 FVMKSPFNNR 206 WYQMGIVSWG216 EGCDRDGKYG226 FYTHVFRLKK236 WIQKVIDQF
|
|||||
|
|
||||||
| PDB ID: 2ZI2 Thrombin Inhibition | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [2] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETGQP152 SVLQVVNLPI 162 VERPVCKDST172 RIRITDNMFC182 AGYKPDEGKR187 GDACEGDSGG197 PFVMKSPFNN 205 RWYQMGIVSW215 GEGCDRDGKY225 GFYTHVFRLK235 KWIQKVIDQF245 |
|||||
|
|
||||||
| PDB ID: 2ZIQ Thrombin Inhibition | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [3] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETGQP152 SVLQVVNLPI 162 VERPVCKDST172 RIRITDNMFC182 AGYKPDEGKR187 GDACEGDSGG197 PFVMKSPFNN 205 RWYQMGIVSW215 GEGCDRDGKY225 GFYTHVFRLK235 KWIQKVIDQF245 G |
|||||
|
|
||||||
| PDB ID: 2ZFQ Exploring thrombin S3 pocket | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [4] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETGQP152 SVLQVVNLPI 162 VERPVCKDST172 RIRITDNMFC182 AGYKPDEGKR187 GDACEGDSGG197 PFVMKSPFNN 205 RWYQMGIVSW215 GEGCDRDGKY225 GFYTHVFRLK235 KWIQKVIDQF245 G |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BEN or .BEN2 or .BEN3 or :3BEN;style chemicals stick;color identity;select .H:170 or .H:171 or .H:172 or .H:217 or .H:223 or .H:224; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 1C5O STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [5] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETGQP152 SVLQVVNLPI 162 VERPVCKDST172 RIRITDNMFC182 AGYKPDEGKR187 GDACEGDSGG197 PFVMKSPFNN 205 RWYQMGIVSW215 GEGCDRDGKY225 GFYTHVFRLK235 KWIQKVIDQF245 GE |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BEN or .BEN2 or .BEN3 or :3BEN;style chemicals stick;color identity;select .H:57 or .H:189 or .H:190 or .H:191 or .H:192 or .H:193 or .H:194 or .H:195 or .H:196 or .H:213 or .H:214 or .H:215 or .H:216 or .H:217 or .H:219 or .H:220 or .H:221 or .H:225 or .H:226 or .H:227 or .H:228; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
HIS57
4.455
ASP189
1.969
ALA190
2.524
CYS191
3.297
GLU192
3.537
GLY193
4.708
ASP194
4.435
SER195
2.165
GLY196
4.887
VAL213
2.009
SER214
3.746
|
|||||
| PDB ID: 3P70 Structural basis of thrombin-mediated factor V activation: essential role of the hirudin-like sequence Glu666-Glu672 for processing at the heavy chain-B domain junction | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [6] |
| PDB Sequence |
IVEGSDAEIG
373 MSPWQVMLFR383 KSPQELLCGA393 SLISDRWVLT403 AAHCLLYPPW413 DKNFTENDLL 423 VRIGKHSRTR433 YERNIEKISM443 LEKIYIHPRY453 NWRENLDRDI463 ALMKLKKPVA 473 FSDYIHPVCL483 PDRETAASLL493 QAGYKGRVTG503 WGNLKEKGQP520 SVLQVVNLPI 530 VERPVCKDST540 RIRITDNMFC550 AGYKPDEGKR560 GDACEGDSGG570 PFVMKSPFNN 580 RWYQMGIVSW590 GEGCDRDGKY600 GFYTHVFRLK610 KWIQKVIDQF620 GE |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BEN or .BEN2 or .BEN3 or :3BEN;style chemicals stick;color identity;select .B:562 or .B:563 or .B:564 or .B:565 or .B:568 or .B:588 or .B:589 or .B:590 or .B:591 or .B:592 or .B:593 or .B:594 or .B:600 or .B:601 or .B:602; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 1DWB CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS | ||||||
| Method | X-ray diffraction | Resolution | 3.16 Å | Mutation | No | [7] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETWTA149A NVGKGQPSVL 155 QVVNLPIVER165 PVCKDSTRIR175 ITDNMFCAGY184A KPDEGKRGDA190 CEGDSGGPFV 200 MKSPFNNRWY208 QMGIVSWGEG219 CDRDGKYGFY228 THVFRLKKWI238 QKVIDQFG |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BEN or .BEN2 or .BEN3 or :3BEN;style chemicals stick;color identity;select .H:189 or .H:190 or .H:191 or .H:192 or .H:195 or .H:213 or .H:214 or .H:215 or .H:216 or .H:217 or .H:219 or .H:220 or .H:226 or .H:227 or .H:228; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 4UEH Thrombin in complex with benzamidine | ||||||
| Method | X-ray diffraction | Resolution | 1.16 Å | Mutation | No | [8] |
| PDB Sequence |
IVEGSDAEIG
25 MSPWQVMLFR35 KSPQELLCGA44 SLISDRWVLT54 AAHCLLYPPW60D DKNFTENDLL 65 VRIGKHSRTR75 YERNIEKISM84 LEKIYIHPRY94 NWRENLDRDI103 ALMKLKKPVA 113 FSDYIHPVCL123 PDRETAASLL130 QAGYKGRVTG140 WGNLKETWGQ151 PSVLQVVNLP 161 IVERPVCKDS171 TRIRITDNMF181 CAGYKPDEGK186D RGDACEGDSG196 GPFVMKSPFN 204B NRWYQMGIVS214 WGEGCDRDGK224 YGFYTHVFRL234 KKWIQKVIDQ244 FG |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BEN or .BEN2 or .BEN3 or :3BEN;style chemicals stick;color identity;select .H:57 or .H:189 or .H:190 or .H:191 or .H:192 or .H:195 or .H:213 or .H:214 or .H:215 or .H:216 or .H:217 or .H:219 or .H:220 or .H:221 or .H:226 or .H:227 or .H:228; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Understanding Thrombin Inhibition | ||||
| REF 2 | Non-additivity of functional group contributions in protein-ligand binding: a comprehensive study by crystallography and isothermal titration calorimetry. J Mol Biol. 2010 Apr 9;397(4):1042-54. | ||||
| REF 3 | Understanding Thrombin Inhibition | ||||
| REF 4 | Exploring thrombin S3 pocket | ||||
| REF 5 | Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. Chem Biol. 2000 Apr;7(4):299-312. | ||||
| REF 6 | Structural basis of thrombin-mediated factor V activation: the Glu666-Glu672 sequence is critical for processing at the heavy chain-B domain junction. Blood. 2011 Jun 30;117(26):7164-73. | ||||
| REF 7 | Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors. J Biol Chem. 1991 Oct 25;266(30):20085-93. | ||||
| REF 8 | Fragment Binding Can Be Either More Enthalpy-Driven or Entropy-Driven: Crystal Structures and Residual Hydration Patterns Suggest Why. J Med Chem. 2015 Sep 10;58(17):6960-71. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.