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DTSTAMP:20181015T181546
DTSTART;TZID=America/Detroit:20181015T160000
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SUMMARY:Other:Moving beyond Methionine Synthase: New Insights into Cobalamin-Dependent Methyltransferase Reactions
DESCRIPTION:                                   Biological methylation underpins myriad cellular processes through the modification of proteins\, lipids\, nucleic acids\, heavy metals\, and a variety of small organic molecules. In the vast majority of these reactions\, the appended methyl group derives from S-adenosylmethionine (SAM) and is attached most often to nitrogen and oxygen nucleophiles through a polar SN2 mechanism\, although carbon\, sulfur\, and a variety of other nucleophilic atoms also receive SAM-derived methyl groups. Recently\, it has become apparent that SAM is used to methylate non-reactive carbon and phosphorus atoms by mechanisms involving radical intermediates. To date\, these reactions are catalyzed exclusively by radical SAM enzymes\, a superfamily of enzymes that use an iron-sulfur (Fe-S) cluster to catalyze a reductive cleavage of SAM to methionine and the potent oxidant 5’-deoxyadenosin 5’-radical (5’-dA•). There are at least five subclasses of radical SAM methylases. Class B methylases represent the largest subclass\, and use cobalamin to methylate both sp2- and sp3-hybridized carbon centers or phosphinate phosphorus centers during the biosynthesis of numerous biomolecules\, including natural products with antibiotic and anticancer activities. This lecture will focus on two Class B radical SAM methylases involved in the biosynthesis of antibacterial agents. Fom3\, which performs a key step in the biosynthesis of the broad-spectrum antibiotic fosfomycin\, catalyzes the methylation of the sp3-hybridized C2’’ carbon of cytidylyl-2-hydroxyethylphosphonate to yield cytidylyl-2-hydroxypropylphosphonate. By contrast\, TsrM catalyzes the first committed step in the biosynthesis of the quinaldic acid moiety of the thiopeptide antibiotic thiostrepton\, which is the methylation of the sp2-hybridized C2 carbon of the indole ring of L-tryptophan. As will be discussed\, while both Fom3 and TsrM are cobalamin-dependent radical SAM methylases\, they use two distinctly different strategies to catalyze their reactions.                                                                                                                                                             \n                       \n                                                \n                       \n                                                \n                       \n                                                \n                       \n                                                \n                       \n                                                \n                       \n                                                \n                       \n                        \nSquire Booker (The Pennsylvania State University)
UID:51068-11953412@events.umich.edu
URL:https://events.umich.edu/event/51068
CLASS:PUBLIC
STATUS:CONFIRMED
CATEGORIES:Chemistry,Science
LOCATION:Chemistry Dow Lab - Chem 1640
CONTACT:
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