Structural highlights
Function
[NHAA_PSETH] NHase catalyzes the hydration of various nitrile compounds to the corresponding amides. [NHAB_PSETH] NHase catalyzes the hydration of various nitrile compounds to the corresponding amides.
Publication Abstract from PubMed
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 A 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 alphaCys(113)-OH sulfenic acid ligand. Based on these data, a new mechanism of action for the hydration of nitriles by NHase is presented.
The active site sulfenic acid ligand in nitrile hydratases can function as a nucleophile.,Martinez S, Wu R, Sanishvili R, Liu D, Holz R J Am Chem Soc. 2014 Jan 29;136(4):1186-9. doi: 10.1021/ja410462j. Epub 2014 Jan, 13. PMID:24383915[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2014 Jan 29;136(4):1186-9. doi: 10.1021/ja410462j. Epub 2014 Jan, 13. PMID:24383915 doi:http://dx.doi.org/10.1021/ja410462j
