PDBsum entry 3tu7

Hydrolase/hydrolase inhibitor

PDB id: 3tu7

Contents

Protein chains

31 a.a.

250 a.a.

11 a.a.

Ligands

0BM

Waters ×44

PDB id:

3tu7

Name:

Hydrolase/hydrolase inhibitor

Title:

Human alpha-thrombin complexed with n-(methylsulfonyl)-d-phenylalanyl- n-((1-carbamimidoyl-4-piperidinyl)methyl)-l-prolinamide (bms-189664)

Structure:

Prothrombin. Chain: l. Fragment: thrombin light chain. Synonym: coagulation factor ii, activation peptide fragment 1, activation peptide fragment 2, thrombin light chain, thrombin heavy chain. Prothrombin. Chain: h. Fragment: thrombin heavy chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma. Hirudo medicinalis. Medicinal leech. Organism_taxid: 6421. Tissue: plasma

Resolution:

2.49Å R-factor: 0.163 R-free: 0.230

Authors:

M.Malley,J.S.Sack

Key ref:

J.Das et al. (2002). Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664. Bioorg Med Chem Lett, 12, 45-49. PubMed id: 11738570

Date:

16-Sep-11 Release date: 12-Oct-11

Protein chain

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 31 a.a.

Protein chain

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 250 a.a.

Protein chain

P01050  (HIRV1_HIRME) -  Hirudin variant-1 from Hirudo medicinalis

Seq: 65 a.a.

Struc: 11 a.a.

Enzyme reactions

• Enzyme class: Chains L, H: E.C.3.4.21.5 - thrombin.
• Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

Bioorg Med Chem Lett 12:45-49 (2002)

PubMed id: 11738570

Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

J.Das, S.D.Kimball, S.E.Hall, W.C.Han, E.Iwanowicz, J.Lin, R.V.Moquin, J.A.Reid, J.S.Sack, M.F.Malley, C.Y.Chang, S.Chong, D.B.Wang-Iverson, D.G.Roberts, S.M.Seiler, W.A.Schumacher, M.L.Ogletree.

ABSTRACT

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.