PDBsum entry 2vh6

Hydrolase

PDB id: 2vh6

Contents

Protein chains

232 a.a. *

54 a.a. *

Ligands

GSV

Waters ×171

* Residue conservation analysis

PDB id:

2vh6

Name:

Hydrolase

Title:

Structure and property based design of factor xa inhibitors: pyrrolidin-2-ones with biaryl p4 motifs

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: purchased from enzyme research labs. Isolated from human blood. Human blood

Resolution:

1.95Å R-factor: 0.199 R-free: 0.242

Authors:

R.J.Young,A.D.Borthwick,D.Brown,C.L.Burns-Kurtis,M.Campbell,C.Chan, M.Charbaut,C.W.Chung,M.A.Convery,H.A.Kelly,N.P.King,S.Kleanthous, A.M.Mason,A.J.Pateman,A.N.Patikis,I.L.Pinto,D.R.Pollard,S.Senger, G.P.Shah,J.R.Toomey,N.S.Watson,H.E.Weston

Key ref:

R.J.Young et al. (2008). Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs. Bioorg Med Chem Lett, 18, 23-27. PubMed id: 18054228

Date:

19-Nov-07 Release date: 16-Dec-08

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 232 a.a.

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 54 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: 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 18:23-27 (2008)

PubMed id: 18054228

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs.

R.J.Young, A.D.Borthwick, D.Brown, C.L.Burns-Kurtis, M.Campbell, C.Chan, M.Charbaut, C.W.Chung, M.A.Convery, H.A.Kelly, N.Paul King, S.Kleanthous, A.M.Mason, A.J.Pateman, A.N.Patikis, I.L.Pinto, D.R.Pollard, S.Senger, G.P.Shah, J.R.Toomey, N.S.Watson, H.E.Weston.

ABSTRACT

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.