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dc.contributor.authorScheuring, Eva
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 56-10, Section: B, page: 5371.
dc.description.abstractCobalamin dependent enzymes participate in a number of carbon skeleton rearrangement reactions as well as methylation reactions essential to all mammals. The key step in all of these reactions is the breakage of the Co-C bond. In the methylation reactions, utilizing methylcobalamin, the cofactor is cycling between Co(I) and Co(III)-methyl states, while the rearrangement reactions, utilizing 5'-deoxyadenosylcobalamin as cofactor, appear dependent on free radical transfer to substrate mediated through homolytic cobalt-carbon cleavage and formation of a Co(II) species. The 5,6-dimethylbenzimidazole group (DMB or base), connected to the Co atom on the opposite side of the Co-C bond, is generally believed to have a significant role modulating the Co-C bond cleavage. The base-on/base-off configuration has a proven effect on favoring homolytic versus heterolytic cleavage. However, recent crystallographic data on the 27 kDa fragment of methionine synthase, a methylcobalamin dependent enzyme, shows that the DMB ligand is replaced by a histidine group of the enzyme. Interestingly, there is a conserved region in other cobalamin dependent enzymes containing a histidine residue in the same position.;Using different spectroscopic techniques, primarily X-ray absorption spectroscopy (XAS) we have been intensively studying different forms of the free cobalamins and also the enzyme bound complexes, addressing the possibility of histidine replacement and changes in the cofactor structure upon binding to the enzyme. We have also made significant improvements in time-resolved pump-probe XAS (TRXAS); such methods are able to detect dynamic changes of metal centers as the reaction of interest proceeds and structurally describe short-lived intermediates in cases where other spectroscopies may only give indirect structural information. Our TRXAS studies on the primary photoproduct of base-off methylcobalamin demonstrate our ability to follow the structural dynamics of an enzymatically important species. In combination with our static XAS results on free and enzyme bound cobalamins these studies give new insight into the understanding of the enzyme's role accelerating the Co-C bond cleavage and promoting the homolytic versus heterolytic cleavage mechanism.
dc.publisherProQuest Dissertations & Theses
dc.titleStructural and electronic effects in cobalamins and model compounds: Their importance in the enzymatic processes

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