PDBsum entry 1g3c

Hydrolase

PDB id: 1g3c

Contents

Protein chain

223 a.a. *

Ligands

SO4

109 ×2

Metals

_FE

_CA

Waters ×174

* Residue conservation analysis

PDB id:

1g3c

Name:

Hydrolase

Title:

Bovine beta-trypsin bound to para-amidino schiff base iron(iii) chelate

Structure:

Beta-trypsin. Chain: a. Fragment: mature enzyme. Ec: 3.4.21.4

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Secretion: pancreas

Resolution:

1.80Å R-factor: 0.172 R-free: 0.188

Authors:

E.Toyota,K.K.S.Ng,H.Sekizaki,K.Itoh,K.Tanizawa,M.N.G.James

Key ref:

E.Toyota et al. (2001). X-ray crystallographic analyses of complexes between bovine beta-trypsin and Schiff base copper(II) or iron(III) chelates. J Mol Biol, 305, 471-479. PubMed id: 11152605 DOI: 10.1006/jmbi.2000.4303

Date:

23-Oct-00 Release date: 17-Jan-01

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.

DOI no: 10.1006/jmbi.2000.4303

J Mol Biol 305:471-479 (2001)

PubMed id: 11152605

X-ray crystallographic analyses of complexes between bovine beta-trypsin and Schiff base copper(II) or iron(III) chelates.

E.Toyota, K.K.Ng, H.Sekizaki, K.Itoh, K.Tanizawa, M.N.James.

ABSTRACT

To establish the structural basis underlying the activity of a novel series of metal-chelate trypsin inhibitors, the structures of p-amidinosalicylidene-l-alaninato(aqua)copper(II) (1a), m-amidinosalicylidene-l-alaninato(aqua)copper(II) (1b), bis(p-amidinosalicylidene-l-alaninato)iron(III) (2a), and bis(m-amidinosalicylidene-l-alaninato)iron(III) (2b) bound to bovine beta-trypsin were studied by X-ray crystallography. The amidinium group of the inhibitor donates hydrogen bonds to Asp189, Gly219 and Ser190, as seen before in trypsin-benzamidine complexes. The copper(II) ion of 1a is situated away from trypsin's catalytic triad residues, and is octahedrally coordinated by a Schiff base and three water molecules. In contrast, the copper(II) ion of 1b is situated close to the catalytic triad and adopts a square pyramidal coordination geometry. The iron(III) ion of 2a is octahedrally coordinated by two Schiff base ligands and, like the copper(II) ion of 1a, is situated away from the catalytic triad. The p-amidinophenyl ring of a second Schiff base ligand of 2a is directed toward a hydrophobic groove formed by Trp215 and Leu99. Finally, the iron(III) ion of 2b appears to be replaced by magnesium(II), which is octahedrally coordinated by a Schiff base, Gln192 and two water molecules. One of the Schiff base ligands seen in the trypsin-2a complex or in the unbound form of 2b is replaced by water molecules and Gln192. His57 and Ser195 form water-mediated interactions with the magnesium(II) ion of 2b, and Ser195 also forms a hydrogen bond with the phenolic oxygen atom of the Schiff base ligand. These structures reveal a novel mode of interaction between metal-chelate inhibitors and serine proteases, thus providing a structural basis for the development of more potent inhibitors against a variety of trypsin-like enzymes.

Selected figure(s)

Figure 1.
Figure 1. Chemical formulae of the inhibitors used in this study.

Figure 3.
Figure 3. Schematic representation of metal coordination geometry and hydrogen bonds of trypsin-1a (a), trypsin-1b (b), trypsin-2a (c) and trypsin-2b (d) complexes in the region of active site. Hydrogen bonds between inhibitor and trypsin are drawn in broken lines.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 305, 471-479) copyright 2001.

Figures were selected by an automated process.