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dc.contributor.authorHAZRA, AMRITA B.en_US
dc.contributor.authorBallou, David P.en_US
dc.contributor.authorTag, Michiko E.en_US
dc.date.accessioned2019-09-11T05:05:25Z
dc.date.available2019-09-11T05:05:25Z
dc.date.issued2018-02en_US
dc.identifier.citationBiochemistry, 57(1), 11748-1757.en_US
dc.identifier.issnJun-60en_US
dc.identifier.issn1520-4995en_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/4065-
dc.identifier.urihttps://doi.org/10.1021/acs.biochem.7b01193en_US
dc.description.abstractVitamin B12 (cobalamin) is an essential micronutrient for humans that is synthesized by only a subset of bacteria and archaea. The aerobic biosynthesis of 5,6-dimethylbenzimidazole, the lower axial ligand of cobalamin, is catalyzed by the “flavin destructase” enzyme BluB, which fragments reduced flavin mononucleotide following its reaction with oxygen to yield this ligand. BluB is similar in sequence and structure to members of the flavin oxidoreductase superfamily, yet the flavin destruction process has remained elusive. Using stopped-flow spectrophotometry, we find that the flavin destructase reaction of BluB from Sinorhizobium meliloti is initiated with canonical flavin–O2 chemistry. A C4a-peroxyflavin intermediate is rapidly formed in BluB upon reaction with O2, and has properties similar to those of flavin-dependent hydroxylases. Analysis of reaction mixtures containing flavin analogues indicates that both formation of the C4a-peroxyflavin and the subsequent destruction of the flavin to form 5,6-dimethylbenzimidazole are influenced by the electronic properties of the flavin isoalloxazine ring. The flavin destruction phase of the reaction, which results from the decay of the C4a-peroxyflavin intermediate, occurs more efficiently at pH >7.5. Furthermore, the BluB mutants D32N and S167G are specifically impaired in the flavin destruction phase of the reaction; nevertheless, both form the C4a-peroxyflavin nearly quantitatively. Coupled with a phylogenetic analysis of BluB and related flavin-dependent enzymes, these results demonstrate that the BluB flavin destructase family can be identified by the presence of active site residues D32 and S167.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.subjectVitamin B12en_US
dc.subjectMicronutrient for humansen_US
dc.subjectSynthesizeden_US
dc.subjectBacteria and archaeaen_US
dc.subject2018en_US
dc.titleUnique Biochemical and Sequence Features Enable BluB To Destroy Flavin and Distinguish BluB from the Flavin Monooxygenase Superfamilyen_US
dc.typeArticleen_US
dc.contributor.departmentDept. of Chemistryen_US
dc.identifier.sourcetitleBiochemistryen_US
dc.publication.originofpublisherForeignen_US
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