PDBsum entry 2cji

Hydrolase

PDB id

2cji

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Contents

			Protein chains

					234 a.a. *


					52 a.a. *

			Ligands

					GSK

			Metals

					_CA

			Waters ×143

* Residue conservation analysis

PDB id:

2cji

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Name:

Hydrolase

Title:

Crystal structure of a human factor xa inhibitor complex

Structure:

Activated factor xa heavy chain. Chain: a. Fragment: activated desgla, residues 235-488. Synonym: coagulation factor xa. Other_details: disulphide linked to other chain. Factor x light chain. Chain: b. Fragment: activated desgla, residues 46-179. Synonym: coagulation factor xa.

Source:

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

Biol. unit:

Dimer (from PDB file)

Resolution:

2.10Å

R-factor:

0.195

R-free:

0.242

Authors:

N.S.Watson,M.Campbell,C.Chan,M.A.Convery,J.N.Hamblin,H.A.Kelly, N.P.King,A.M.Mason,C.Mitchell,V.K.Patel,S.Senger,G.P.Shah, H.E.Weston,C.Whitworth,R.J.Young

Key ref:

N.S.Watson et al. (2006). Design and synthesis of orally active pyrrolidin-2-one-based factor Xa inhibitors. Bioorg Med Chem Lett, 16, 3784-3788. PubMed id: 16697194 DOI: 10.1016/j.bmcl.2006.04.053

Date:

03-Apr-06

Release date:

17-May-06

PROCHECK

	Headers

	References

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 234 a.a.

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 52 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

Chains A, B: E.C.3.4.21.6 - coagulation factor Xa.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

DOI no: 10.1016/j.bmcl.2006.04.053	Bioorg Med Chem Lett 16:3784-3788 (2006)
PubMed id: 16697194

Design and synthesis of orally active pyrrolidin-2-one-based factor Xa inhibitors.
N.S.Watson, D.Brown, M.Campbell, C.Chan, L.Chaudry, M.A.Convery, R.Fenwick, J.N.Hamblin, C.Haslam, H.A.Kelly, N.P.King, C.L.Kurtis, A.R.Leach, G.R.Manchee, A.M.Mason, C.Mitchell, C.Patel, V.K.Patel, S.Senger, G.P.Shah, H.E.Weston, C.Whitworth, R.J.Young.

ABSTRACT

A series of novel, non-basic 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group, was designed and synthesised. Within this series, the N-2-(morpholin-4-yl)-2-oxoethyl derivative 24 was shown to be a potent, selective fXa inhibitor with good anticoagulant activity. Moreover, 24 possessed highly encouraging rat and dog pharmacokinetic profiles with excellent oral bioavailabilities in both species.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19967784

Y.K.Lee, and M.R.Player (2011).
Developments in factor Xa inhibitors for the treatment of thromboembolic disorders.

Med Res Rev, 31, 202-283.

18645410

M.A.Abboud, S.J.Needle, C.L.Burns-Kurtis, R.E.Valocik, P.F.Koster, A.J.Amour, C.Chan, D.Brown, L.Chaudry, P.Zhou, A.Patikis, C.Patel, A.J.Pateman, R.J.Young, N.S.Watson, and J.R.Toomey (2008).
Antithrombotic potential of GW813893: a novel, orally active, active-site directed factor Xa inhibitor.

J Cardiovasc Pharmacol, 52, 66-71.

18266362

R.Abel, T.Young, R.Farid, B.J.Berne, and R.A.Friesner (2008).
Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.

J Am Chem Soc, 130, 2817-2831.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.