1MTV

FACTOR XA SPECIFIC INHIBITOR IN COMPLEX WITH BOVINE TRYPSIN

Summary for 1MTV

• Entry DOI: 10.2210/pdb1mtv/pdb
• Related: 1MTS 1MTU 1MTW
• Descriptor: TRYPSIN, CALCIUM ION, (+)-2-[4-[(-1-ACETIMIDOYL-4-PIPERIDINYL)OXY]-3-(7-AMIDINO-2-NAPHTHYL)PROPIONIC ACID, ... (4 entities in total)
• Functional Keywords: hydrolase, serine protease
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 23822.92

Authors

Stubbs, M.T. (deposition date: 1997-05-16, release date: 1997-11-12, Last modification date: 2024-10-23)

Primary citation

Stubbs, M.T.,Huber, R.,Bode, W.
Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin.
FEBS Lett., 375:103-107, 1995

PubMed Abstract: Crystal structures of DX9065a and a related bisamidino-aryl inhibitor specific for the blood-clotting factor Xa have been solved in complex with bovine beta-trypsin to a resolution of 1.9 A. Each inhibitor exhibits an extended conformation along the active site, in contrast to the compact folded structures observed for thrombin specific inhibitors. Few direct contacts (predominantly in the S1 pocket) are made between trypsin and the inhibitors. Transfer of the inhibitors to the active site of factor Xa suggests a three-site interaction: salt bridge formation at the base of the primary specificity pocket, extensive hydrophobic surface burial and a weak electrostatic interaction between the distal basic component of the inhibitor and an electronegative cavity of factor Xa formed by three backbone carbonyl oxygens. Additivity of these three interactions is the basis for the observed strong inhibition of factor Xa and provides a framework for the design of novel factor Xa inhibitors. A propionic acid group of the inhibitor would clash with the thrombin specific '60-insertion loop', thus conferring selectivity against thrombin.

PubMed: 7498454
DOI: 10.1016/0014-5793(95)01190-P

Experimental method

X-RAY DIFFRACTION (1.9 Å)