Structure of PDB 2xbx Chain A Binding Site BS01

Receptor Information

>2xbx Chain A (length=234) Species: 9606 (Homo sapiens)

IVGGQECKDGECPWQALLINEENEGFCGGTILSEFYILTAAHCLYQAKRF
KVRVGDRNTEQEEGGEAVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITF
RMNVAPACLPERDWAESTLMTQKTGIVSGFGRTHEKGRQSTRLKMLEVPY
VDRNSCKLSSSFIITQNMFCAGYDTKQEDACQGDSGGPHVTRFKDTYFVT
GIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKT

Ligand information

• Ligand ID: RR8
• InChI: InChI=1S/C24H22ClFN4O5S/c1-36(34,35)29-13-18(23(32)27-16-7-5-15(25)6-8-16)19(14-29)24(33)28-21-10-9-17(12-20(21)26)30-11-3-2-4-22(30)31/h2-12,18-19H,13-14H2,1H3,(H,27,32)(H,28,33)/t18-,19-/m0/s1
• InChIKey: CUZHVTKMXOGVKA-OALUTQOASA-N
• SMILES:
  CACTVS 3.352: C[S](=O)(=O)N1C[CH]([CH](C1)C(=O)Nc2ccc(cc2F)N3C=CC=CC3=O)C(=O)Nc4ccc(Cl)cc4
  CACTVS 3.352: C[S](=O)(=O)N1C[C@@H]([C@H](C1)C(=O)Nc2ccc(cc2F)N3C=CC=CC3=O)C(=O)Nc4ccc(Cl)cc4
  ACDLabs 10.04: O=C(Nc2ccc(N1C=CC=CC1=O)cc2F)C4C(C(=O)Nc3ccc(Cl)cc3)CN(S(=O)(=O)C)C4
  OpenEye OEToolkits 1.6.1: CS(=O)(=O)N1CC(C(C1)C(=O)Nc2ccc(cc2F)N3C=CC=CC3=O)C(=O)Nc4ccc(cc4)Cl
  OpenEye OEToolkits 1.6.1: CS(=O)(=O)[N@]1C[C@@H]([C@H](C1)C(=O)Nc2ccc(cc2F)N3C=CC=CC3=O)C(=O)Nc4ccc(cc4)Cl
• Formula: C24 H22 Cl F N4 O5 S
• Name: (3R,4R)-1-METHANESULFONYL-PYRROLIDINE-3,4-DICARBOXYLIC ACID 3-[(4-CHLORO-PHENYL)-AMIDE] 4-{[2-FLUORO-4-(2-OXO-2H-PYRIDIN-1-YL)-PHENYL]-AMIDE}
• ChEMBL: CHEMBL1221534
• ZINC: ZINC000014210918
• PDB chain: 2xbx Chain A Residue 1245

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2xbx Discovery of a Factor Xa Inhibitor (3R,4R)-1-(2,2-Difluoro-Ethyl)-Pyrrolidine-3,4-Dicarboxylic Acid 3-[(5-Chloro-Pyridin-2-Yl)-Amide] 4-{[2-Fluoro-4-(2-Oxo-2H-Pyridin-1-Yl)-Phenyl]-Amide} as a Clinical Candidate.
• Resolution: 1.85 Å
• Binding residue (original residue number in PDB): E97 T98 Y99 E147 F174 D189 A190 Q192 V213 W215 G216 G218 C220 G226 I227 Y228
• Binding residue (residue number reindexed from 1): E83 T84 Y85 E135 F162 D179 A180 Q182 V203 W205 G206 G208 C209 G216 I217 Y218
• Annotation score: 1
• Binding affinity: MOAD: Ki=0.015uM
  PDBbind-CN: -logKd/Ki=7.82,Ki=15nM
  BindingDB: Ki=15nM

Enzymatic activity

• Catalytic site (original residue number in PDB): H57 D102 Q192 G193 D194 S195 G196
• Catalytic site (residue number reindexed from 1): H42 D88 Q182 G183 D184 S185 G186
• Enzyme Commision number: 3.4.21.6: coagulation factor Xa.

Gene Ontology

Molecular Function

• GO:0004252 serine-type endopeptidase activity

Biological Process

• GO:0006508 proteolysis

External links

• PDB: RCSB:2xbx, PDBe:2xbx, PDBj:2xbx
• PDBsum: 2xbx
• PubMed: 20650636
• UniProt: P00742|FA10_HUMAN Coagulation factor X (Gene Name=F10)