1B5G

HUMAN THROMBIN COMPLEXED WITH NOVEL SYNTHETIC PEPTIDE MIMETIC INHIBITOR AND HIRUGEN

Summary for 1B5G

• Entry DOI: 10.2210/pdb1b5g/pdb
• Descriptor: ALPHA-THROMBIN, HIRUGEN, [[[(4S,5S)-4-[[(3S,6S,8aR)-6-azanyl-5-oxo-6-(phenylmethyl)-1,2,3,7,8,8a-hexahydroindolizin-3-yl]carbonylamino]-5-(1,3-b enzothiazol-2-yl)-5-hydroxy-pentyl]amino]-azanyl-methylidene]azanium, ... (6 entities in total)
• Functional Keywords: serine protease-inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P09945; Secreted: P00734
• Total number of polymer chains: 3
• Total formula weight: 36022.01

Authors

St Charles, R.,Tulinsky, A.,Kahn, M. (deposition date: 1998-03-05, release date: 1998-05-27, Last modification date: 2024-06-05)

Primary citation

St Charles, R.,Matthews, J.H.,Zhang, E.,Tulinsky, A.
Bound structures of novel P3-P1' beta-strand mimetic inhibitors of thrombin.
J.Med.Chem., 42:1376-1383, 1999

PubMed Abstract: The X-ray crystal structures of four beta-strand-templated active site inhibitors of thrombin containing P1' groups have been determined and refined at about 2.1-A resolution to crystallographic R-values between 0.148 and 0.164. Two of the inhibitors have an alpha-ketoamide functionality at the scissile bond; the other two have a nonhydrolyzable electrophilic group at the P1' position. The binding of lysine is compared with that of arginine at the S1 specificity site, while that of D,L-phenylalanine enantiomorphs is compared in the S3 region of thrombin. Four different P1' moieties bind at the S1' subsite in three different ways. The binding constants vary between 2.0 microM and 70 pM. The bound structures are used to intercorrelate the various binding constants and also lead to insightful inferences concerning binding at the S1' site of thrombin.

PubMed: 10212123
DOI: 10.1021/jm980052n

Experimental method

X-RAY DIFFRACTION (2.07 Å)