1g3c
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BOVINE BETA-TRYPSIN BOUND TO PARA-AMIDINO SCHIFF BASE IRON(III) CHELATE
OverviewOverview
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.
About this StructureAbout this Structure
1G3C is a Single protein structure of sequence from Bos taurus with FE, CA, SO4 and 109 as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystallographic analyses of complexes between bovine beta-trypsin and Schiff base copper(II) or iron(III) chelates., Toyota E, Ng KK, Sekizaki H, Itoh K, Tanizawa K, James MN, J Mol Biol. 2001 Jan 19;305(3):471-9. PMID:11152605
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