1K2I

Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin

1K2I の概要

• エントリーDOI: 10.2210/pdb1k2i/pdb
• 関連するPDBエントリー: 1GCT
• 分子名称: CHYMOTRYPSINOGEN A, SULFATE ION, 2,4-DIHYDROXY-TRANS CINNAMIC ACID, ... (4 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, hydrolase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted, extracellular space: P00766
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25962.26

構造登録者

Ghani, U.,Ng, K.K.S.,Atta-ur-Rahman,Choudhary, M.I.,Ullah, N.,James, M.N.G. (登録日: 2001-09-27, 公開日: 2001-12-05, 最終更新日: 2023-08-16)

主引用文献

Ghani, U.,Ng, K.K.,Atta-ur-Rahman,Choudhary, M.I.,Ullah, N.,James, M.N.
Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.
J.Mol.Biol., 314:519-525, 2001

PubMed Abstract: The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes.

PubMed: 11846564
DOI: 10.1006/jmbi.2001.5148

実験手法

X-RAY DIFFRACTION (1.8 Å)