3AAS

Bovine beta-trypsin bound to meta-guanidino schiff base copper (II) chelate

Summary for 3AAS

• Entry DOI: 10.2210/pdb3aas/pdb
• Related: 1G3D 3AAU 3AAV
• Descriptor: Cationic trypsin, (E)-N-[(5-carbamimidamido-2-hydroxyphenyl)methylidene]-L-alanine, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: enzyme-inhibitor complex, coordination metal based inhibitor, hydrolase, calcium, digestion, metal-binding, protease, secreted, serine protease, zymogen
• Biological source: Bos taurus (bovine)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 23678.17

Authors

Iyaguchi, D.,Kawano, S.,Toyota, E. (deposition date: 2009-11-26, release date: 2010-04-07, Last modification date: 2024-10-23)

Primary citation

Iyaguchi, D.,Kawano, S.,Takada, K.,Toyota, E.
Structural basis for the design of novel Schiff base metal chelate inhibitors of trypsin
Bioorg.Med.Chem., 18:2076-2080, 2010

PubMed 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.

PubMed: 20202854
DOI: 10.1016/j.bmc.2010.02.016

Experimental method

X-RAY DIFFRACTION (1.75 Å)