PDBsum entry 3aas

Hydrolase

PDB id: 3aas

Contents

Protein chain

223 a.a.

Ligands

GUS

Metals

_CU

_CA

Waters ×275

References listed in PDB file

Key reference

• Title: Structural basis for the design of novel schiff base metal chelate inhibitors of trypsin.
• Authors: D.Iyaguchi, S.Kawano, K.Takada, E.Toyota.
• Ref.: Bioorg Med Chem Lett, 2010, 18, 2076-2080.
• PubMed id: 20202854

Abstract

The crystal structures of the complexes of bovine trypsin with m-guanidinosalicylidene-l-alaninato(aqua)copper(II) hydrochloride (inhibitor 1), [N,N'-bis(m-guanidinosalicylidene)ethylenediaminato]copper(II) (inhibitor 2), and [N,N'-bis(m-amidinosalicylidene)ethylenediaminato]copper(II) (inhibitor 4) have been determined. The guanidine-containing trypsin-inhibitors (1 and 2) bind to the trypsin active site in a manner similar to that previously reported for amidine-containing inhibitors, for example, m-amidinosalicylidene-l-alaninato(aqua)copper(II) hydrochloride (inhibitor 3). However, the binding mode of the guanidino groups of inhibitors 1 and 2 to Asp189 in the S1 pocket of trypsin was found to be markedly different from that of the amidino group of inhibitor 3. The present X-ray analyses revealed that the interactions of the metal ion of the inhibitors with the active site residues of trypsin play a crucial role in the binding affinity to the trypsin molecule. These structural information and inhibitory activity data for amidine- and guanidine-containing Schiff base metal chelate inhibitors provide new avenues for designing novel inhibitors against physiologically important trypsin-like serine proteases.