3dfz | pdb_00003dfz
SirC, precorrin-2 dehydrogenase
Structural highlights
Function[SIRC_BACME] Catalyzes the dehydrogenation of precorrin-2 to form sirohydrochlorin which is used as a precursor in both siroheme biosynthesis and in the anaerobic branch of adenosylcobalamin biosynthesis. It is unable to oxidize precorrin-3.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn 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 A (1 A = 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 an independent chelatase, may provide greater control over the intermediate at this branchpoint in the synthesis of sirohaem and cobalamin. Structure and function of SirC from Bacillus megaterium: a metal-binding precorrin-2 dehydrogenase.,Schubert HL, Rose RS, Leech HK, Brindley AA, Hill CP, Rigby SE, Warren MJ Biochem J. 2008 Oct 15;415(2):257-63. PMID:18588505[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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