1QBN

Bovine Trypsin 2-[amino(imino)methyl]-2-hydroxyphenoxy]-6-[3-(4,5-dihydro-1H-imidazol-2-yl)phenoxy]pyridine-4-carboxylic Acid (ZK-806688) Complex

Summary for 1QBN

• Entry DOI: 10.2210/pdb1qbn/pdb
• Related: 1QA0
• Descriptor: PROTEIN (TRYPSIN), CALCIUM ION, 2-[AMINO(IMINO)METHYL]-2-HYDROXYPHENOXY]-6-[3-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)PHENOXY]PYRIDINE-4-CARBOXYLIC ACID, ... (4 entities in total)
• Functional Keywords: hydrolase, serine proteinase, protein-inhibitor complex, s1 pocket
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 23835.84

Authors

Whitlow, M. (deposition date: 1999-04-25, release date: 2000-05-03, Last modification date: 2024-10-30)

Primary citation

Whitlow, M.,Arnaiz, D.O.,Buckman, B.O.,Davey, D.D.,Griedel, B.,Guilford, W.J.,Koovakkat, S.K.,Liang, A.,Mohan, R.,Phillips, G.B.,Seto, M.,Shaw, K.J.,Xu, W.,Zhao, Z.,Light, D.R.,Morrissey, M.M.
Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin.
Acta Crystallogr.,Sect.D, 55:1395-1404, 1999

PubMed Abstract: Factor Xa is a serine protease which activates thrombin (factor IIa) and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is, therefore, an important target for the design of anti-thrombotics. Both factor Xa and thrombin share sequence and structural homology with trypsin. As part of a factor Xa inhibitor-design program, a number of factor Xa inhibitors were crystallographically studied complexed to bovine trypsin. The structures of one diaryl benzimidazole, one diaryl carbazole and three diaryloxypyridines are described. All five compounds bind to trypsin in an extended conformation, with an amidinoaryl group in the S1 pocket and a second basic/hydrophobic moiety bound in the S4 pocket. These binding modes all bear a resemblance to the reported binding mode of DX-9065a in bovine trypsin and human factor Xa.

PubMed: 10417407
DOI: 10.1107/S0907444999007350

Experimental method

X-RAY DIFFRACTION (1.8 Å)