PDBsum entry 3ffg

Hydrolase

PDB id: 3ffg

Contents

Protein chains

234 a.a. *

52 a.a. *

Ligands

FFG

Waters ×253

* Residue conservation analysis

PDB id:

3ffg

Name:

Hydrolase

Title:

Factor xa in complex with the inhibitor (r)-6-(2'-((3- hydroxypyrrolidin-1-yl)methyl)biphenyl-4-yl)-1-(3-(5-oxo-4,5-dihydro- 1h-1,2,4-triazol-3-yl)phenyl)-3-(trifluoromethyl)-5,6-dihydro-1h- pyrazolo[3,4-c]pyridin- 7(4h)-one

Structure:

Coagulation factor x, heavy chain. Chain: a. Fragment: sequence database residues 235-468. Synonym: factor xa heavy chain, stuart factor, stuart-prower factor, factor x heavy chain. Coagulation factor x, light chain. Chain: l. Fragment: sequence database residues 127-178. Synonym: factor x light chain, stuart factor, stuart-prower factor.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: proteolytic cleavage product

Resolution:

1.54Å R-factor: 0.216 R-free: 0.240

Authors:

R.A.Alexander

Key ref:

M.L.Quan et al. (2010). Phenyltriazolinones as potent factor Xa inhibitors. Bioorg Med Chem Lett, 20, 1373-1377. PubMed id: 20100660

Date:

03-Dec-08 Release date: 08-Dec-09

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 234 a.a.

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 52 a.a.

Enzyme reactions

• Enzyme class: Chains A, L: E.C.3.4.21.6 - coagulation factor Xa.
• Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

Bioorg Med Chem Lett 20:1373-1377 (2010)

PubMed id: 20100660

Phenyltriazolinones as potent factor Xa inhibitors.

M.L.Quan, D.J.Pinto, K.A.Rossi, S.Sheriff, R.S.Alexander, E.Amparo, K.Kish, R.M.Knabb, J.M.Luettgen, P.Morin, A.Smallwood, F.J.Woerner, R.R.Wexler.

ABSTRACT

We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the phenyltriazolinone P1 substrate.