PDBsum entry 2p94

Hydrolase

PDB id: 2p94

Contents

Protein chains

234 a.a. *

52 a.a. *

Ligands

ME4

Waters ×135

* Residue conservation analysis

PDB id:

2p94

Name:

Hydrolase

Title:

Factor xa in complex with the inhibitor 3-chloro-n-((1r,2s)-2-(4-(2- oxopyridin-1(2h)-yl)benzamido)cyclohexyl)-1h-indole-6-carboxamide

Structure:

Factor xa. Chain: a. Fragment: residues 16-244. Synonym: factor xa heavy chain, activated factor xa heavy chain. Factor xa. Chain: l. Fragment: residues 87-138. Synonym: factor xa light chain. Ec: 3.4.21.6

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606

Resolution:

1.80Å R-factor: 0.297 R-free: 0.330

Authors:

C.-H.Chang

Key ref:

J.X.Qiao et al. (2007). SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa. Bioorg Med Chem Lett, 17, 4419-4427. PubMed id: 17588746 DOI: 10.1016/j.bmcl.2007.06.029

Date:

23-Mar-07 Release date: 24-Jul-07

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.

DOI no: 10.1016/j.bmcl.2007.06.029

Bioorg Med Chem Lett 17:4419-4427 (2007)

PubMed id: 17588746

SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa.

J.X.Qiao, C.H.Chang, D.L.Cheney, P.E.Morin, G.Z.Wang, S.R.King, T.C.Wang, A.R.Rendina, J.M.Luettgen, R.M.Knabb, R.R.Wexler, P.Y.Lam.

ABSTRACT

In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.