1BTP

UNIQUE BINDING OF A NOVEL SYNTHETIC INHIBITOR, N-[3-[4-[4-(AMIDINOPHENOXY)-CARBONYL]PHENYL]-2-METHYL-2-PROPENOYL]-N-ALLYLGLYCINE METHANESULFONATE TO BOVINE TRYPSIN, REVEALED BY THE CRYSTAL STRUCTURE OF THE COMPLEX

Summary for 1BTP

• Entry DOI: 10.2210/pdb1btp/pdb
• Descriptor: BETA-TRYPSIN, CALCIUM ION (3 entities in total)
• Functional Keywords: hydrolase (serine proteinase)
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 24053.03

Authors

Odagaki, Y.,Nakai, H.,Senokuchi, K.,Kawamura, M.,Hamanaka, N.,Nakamura, M.,Tomoo, K.,Ishida, T. (deposition date: 1995-08-11, release date: 1996-01-29, Last modification date: 2024-06-05)

Primary citation

Odagaki, Y.,Nakai, H.,Senokuchi, K.,Kawamura, M.,Hamanaka, N.,Nakamura, M.,Tomoo, K.,Ishida, T.
Unique binding of a novel synthetic inhibitor, N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate, to bovine trypsin, revealed by the crystal structure of the complex.
Biochemistry, 34:12849-12853, 1995

PubMed Abstract: Trypsin and N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate (1), a newly designed and orally active synthetic trypsin inhibitor, were cocrystallized. The space group of the crystal is P2(1)2(1)2(1) with cell constants a = 63.74 A, b = 63.08 A, and c = 69.38 A, which is nearly identical to that of the orthorhombic crystal of guanidinobenzoyltrypsin. The structure was refined to a crystallographic residual R = 0.176. The refined model of the 1-trypsin complex provides the structural basis for the reaction mechanism of 1. On the basis of the present X-ray results, it is proposed that the potent inhibitory activity of 1 is mainly due to the formation of an acylated trypsin through an "inverse substrate mechanism" and its low rate of deacylation.

PubMed: 7548040
DOI: 10.1021/bi00039a046

Experimental method

X-RAY DIFFRACTION (2.2 Å)