1SB1

Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics

Summary for 1SB1

• Entry DOI: 10.2210/pdb1sb1/pdb
• Descriptor: Prothrombin, hirugen, SODIUM ION, ... (6 entities in total)
• Functional Keywords: thrombin, inhibition, hirugen, serine protease inhibitor, blood clotting, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734; Secreted: P28504
• Total number of polymer chains: 3
• Total formula weight: 34949.89

Authors

Marinko, P.,Krbavcic, A.,Mlinsek, G.,Solmajer, T.,Trampus-Bakija, A.,Stegnar, M.,Stojan, J.,Kikelj, D. (deposition date: 2004-02-09, release date: 2004-06-08, Last modification date: 2024-11-20)

Primary citation

Marinko, P.,Krbavcic, A.,Mlinsek, G.,Solmajer, T.,Trampus-Bakija, A.,Stegnar, M.,Stojan, J.,Kikelj, D.
Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics
Eur.J.Med.Chem., 39:257-265, 2004

PubMed Abstract: The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.

PubMed: 15051174
DOI: 10.1016/j.ejmech.2003.12.006

Experimental method

X-RAY DIFFRACTION (1.9 Å)