PDBsum entry 3aau

Hydrolase

PDB id: 3aau

Contents

Protein chain

223 a.a. *

Ligands

GZC

Metals

_CU

_CA

Waters ×259

* Residue conservation analysis

PDB id:

3aau

Name:

Hydrolase

Title:

Bovine beta-trypsin bound to meta-diguanidino schiff base copper (ii) chelate

Structure:

Cationic trypsin. Chain: a. Synonym: beta-trypsin. Ec: 3.4.21.4

Source:

Bos taurus. Bovine. Organism_taxid: 9913

Resolution:

1.80Å R-factor: 0.173 R-free: 0.202

Authors:

D.Iyaguchi,S.Kawano,E.Toyota

Key ref:

D.Iyaguchi et al. (2010). Structural basis for the design of novel Schiff base metal chelate inhibitors of trypsin. Bioorg Med Chem Lett, 18, 2076-2080. PubMed id: 20202854

Date:

26-Nov-09 Release date: 07-Apr-10

Protein chain

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

Bioorg Med Chem Lett 18:2076-2080 (2010)

PubMed id: 20202854

Structural basis for the design of novel Schiff base metal chelate inhibitors of trypsin.

D.Iyaguchi, S.Kawano, K.Takada, E.Toyota.

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.