Discovery of Acetylene Hydratase Activity of the Iron-sulphur Protein IspH

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Sep 6

PMID 22948824

Citations 23

Authors

Ingrid Span

Ke Wang

Weixue Wang

Yonghui Zhang

Adelbert Bacher

Wolfgang Eisenreich

Kai Li

Charles Schulz

Eric Oldfield

Michael Groll

Affiliations

Soon will be listed here.

Abstract

The final step of the methylerythritol phosphate isoprenoid biosynthesis pathway is catalysed by the iron-sulphur enzyme IspH, producing the universal precursors of terpenes: isopentenyl diphosphate and dimethylallyl diphosphate. Here we report an unforeseen reaction discovered during the investigation of the interaction of IspH with acetylene inhibitors by X-ray crystallography, Mößbauer, and nuclear magnetic resonance spectroscopy. In addition to its role as a 2H(+)/2e(-) reductase, IspH can hydrate acetylenes to aldehydes and ketones via anti-Markovnikov/Markovnikov addition. The reactions only occur with the oxidised protein and proceed via η(1)-O-enolate intermediates. One of these is characterized crystallographically and contains a C4 ligand oxygen bound to the unique, fourth iron in the 4Fe-4S cluster: this intermediate subsequently hydrolyzes to produce an aldehyde product. This unexpected side to IspH reactivity is of interest in the context of the mechanism of action of other acetylene hydratases, as well as in the design of antiinfectives targeting IspH.

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