Structure and function of SirC from Bacillus megaterium: a metal-binding precorrin-2 dehydrogenase

Schubert, Heidi L. and Rose, Ruth S. and Leech, Helen K. and Brindley, Amanda A. and Hill, Christopher P. and Rigby, Stephen E. J. and Warren, Martin J. (2008) Structure and function of SirC from Bacillus megaterium: a metal-binding precorrin-2 dehydrogenase. Biochemical Journal, 415 . pp. 257-263. ISSN 0264-6021. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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In Bacillus megaterium, the synthesis of vitamin B-12 (cobalamin) and sirohaem diverges at sirohydrochlorin along the branched modified tetrapyrrole biosynthetic pathway. This key intermediate is made by the action of SirC, a precorrin-2 dehydrogenase that requires NAD(+) as a cofactor. The structure of SirC has now been solved by X-ray crystallography to 2.8 angstrom (1 angstrom = 0.1 nm) resolution. The protein is shown to consist of three domains and has a similar topology to the Multifunctional sirohaem synthases Met8p and the N-terminal region of CysG, both of which catalyse not only the dehydrogenation of precorrin-2 but also the ferrochelation of sirohydrochlorin to give sirohaem. Guided by the structure, in the present study a number of active-site residues within SirC were investigated by site-directed mutagenesis. No active-site general base was identified, although surprisingly some of the resulting protein variants were found to have significantly enhanced catalytic activity. Unexpectedly, SirC was found to bind metal ions such as cobalt and copper, and to bind them in an identical fashion with that observed in Met8p. It is suggested that SirC may have evolved from a Met8p-like protein by loss of its chelatase activity. It is proposed that the ability of SirC to act as a single monofunctional enzyme, in conjunction with ail independent chelatase, may provide greater control over the intermediate at this branchpoint in the synthesis of sirohaem and cobalamin.

Item Type: Article
Uncontrolled keywords: chelatase; cobalamin (vitamin B-12); dehydrogenase; precorrin-2; sirohaem; sirohydrochlorin
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Maureen Cook
Date Deposited: 03 Mar 2009 16:09
Last Modified: 17 Jul 2014 13:30
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