3C1K

Crystal structure of thrombin in complex with inhibitor 15

Summary for 3C1K

• Entry DOI: 10.2210/pdb3c1k/pdb
• Descriptor: Prothrombin, Hirugen, 2-{3-[(benzylsulfonyl)amino]-6-methyl-2-oxopyridin-1(2H)-yl}-N-({1-[2-(tert-butylamino)-2-oxoethyl]-4-methyl-1H-imidazol-5-yl}methyl)acetamide, ... (4 entities in total)
• Functional Keywords: thrombin, thrombin inhibitor complex, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, serine protease, zymogen, protease inhibitor, serine protease inhibitor, sulfation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734; Secreted: P28511
• Total number of polymer chains: 2
• Total formula weight: 35114.14

Authors

Yan, Y. (deposition date: 2008-01-23, release date: 2008-03-18, Last modification date: 2024-11-20)

Primary citation

Isaacs, R.C.,Solinsky, M.G.,Cutrona, K.J.,Newton, C.L.,Naylor-Olsen, A.M.,McMasters, D.R.,Krueger, J.A.,Lewis, S.D.,Lucas, B.J.,Kuo, L.C.,Yan, Y.,Lynch, J.J.,Lyle, E.A.
Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles.
Bioorg.Med.Chem.Lett., 18:2062-2066, 2008

PubMed Abstract: Guided by X-ray crystallography of thrombin-inhibitor complexes and molecular modeling, alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridinoneacetamide thrombin inhibitor 1 with various acetamide moieties furnished inhibitors with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency and in vivo antithrombotic efficacy. In the pyrazinoneacetamide series, oral bioavailability was also improved.

PubMed: 18291642
DOI: 10.1016/j.bmcl.2008.01.098

Experimental method

X-RAY DIFFRACTION (1.84 Å)