1G3C

BOVINE BETA-TRYPSIN BOUND TO PARA-AMIDINO SCHIFF BASE IRON(III) CHELATE

1G3C の概要

• エントリーDOI: 10.2210/pdb1g3c/pdb
• 関連するPDBエントリー: 1BTY
• 分子名称: BETA-TRYPSIN, FE (III) ION, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, coordination metal based inhibitor, hydrolase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted, extracellular space: P00760
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24580.32

構造登録者

Toyota, E.,Ng, K.K.S.,Sekizaki, H.,Itoh, K.,Tanizawa, K.,James, M.N.G. (登録日: 2000-10-23, 公開日: 2001-01-17, 最終更新日: 2024-10-30)

主引用文献

Toyota, E.,Ng, K.K.,Sekizaki, H.,Itoh, K.,Tanizawa, K.,James, M.N.
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, 2001

PubMed 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.

PubMed: 11152605
DOI: 10.1006/jmbi.2000.4303

実験手法

X-RAY DIFFRACTION (1.8 Å)