4OB1

Crystal Structure of Nitrile Hydratase from Pseudonocardia thermophila bound to Butaneboronic Acid via Co-crystallization

4OB1 の概要

• エントリーDOI: 10.2210/pdb4ob1/pdb
• 関連するPDBエントリー: 4OB0 4OB2 4OB3
• 分子名称: Cobalt-containing nitrile hydratase subunit alpha, Cobalt-containing nitrile hydratase subunit beta, COBALT (II) ION, ... (5 entities in total)
• 機能のキーワード: nitrile hydratase, nulceophile, hydrolase
• 由来する生物種: Pseudonocardia thermophila; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59805.40

構造登録者

Rui, W.,Salette, M.,Ruslan, S.,Richard, H.,Dali, L. (登録日: 2014-01-06, 公開日: 2014-11-26, 最終更新日: 2024-11-20)

主引用文献

Martinez, S.,Wu, R.,Sanishvili, R.,Liu, D.,Holz, R.
The active site sulfenic acid ligand in nitrile hydratases can function as a nucleophile.
J.Am.Chem.Soc., 136:1186-1189, 2014

PubMed Abstract: Nitrile hydratase (NHase) catalyzes the hydration of nitriles to their corresponding commercially valuable amides at ambient temperatures and physiological pH. Several reaction mechanisms have been proposed for NHase enzymes; however, the source of the nucleophile remains a mystery. Boronic acids have been shown to be potent inhibitors of numerous hydrolytic enzymes due to the open shell of boron, which allows it to expand from a trigonal planar (sp(2)) form to a tetrahedral form (sp(3)). Therefore, we examined the inhibition of the Co-type NHase from Pseudonocardia thermophila JCM 3095 (PtNHase) by boronic acids via kinetics and X-ray crystallography. Both 1-butaneboronic acid (BuBA) and phenylboronic acid (PBA) function as potent competitive inhibitors of PtNHase. X-ray crystal structures for BuBA and PBA complexed to PtNHase were solved and refined at 1.5, 1.6, and 1.2 Å resolution. The resulting PtNHase-boronic acid complexes represent a "snapshot" of reaction intermediates and implicate the cysteine-sulfenic acid ligand as the catalytic nucleophile, a heretofore unknown role for the αCys(113)-OH sulfenic acid ligand. Based on these data, a new mechanism of action for the hydration of nitriles by NHase is presented.

PubMed: 24383915
DOI: 10.1021/ja410462j

実験手法

X-RAY DIFFRACTION (1.631 Å)