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Publication Abstract from PubMed

The methyl substituents in products of trans-acyltransferase assembly lines are usually incorporated by S-adenosyl-methionine (SAM)-dependent methyltransferase (MT) domains. The gem-dimethyl moieties within the polyketide disorazol are installed through the iterative action of an MT in the third module of its assembly line. The 1.75-A-resolution crystal structure of this MT helps elucidate how it catalyzes the addition of two methyl groups. Activity assays of point mutants on beta-ketoacyl chains linked to an acyl carrier protein and N-acetylcysteamine provide additional insights into the roles of active site residues. The replacement of an alanine with a phenylalanine at an apparent gatekeeping position resulted in more monomethylation than dimethylation. MTs may form an interface with ketoreductases (KRs) and even mediate the docking of trans-acyltransferase assembly line polypeptides through this association.

Structural and Functional Studies of a gem-Dimethylating Methyltransferase from a trans-Acyltransferase Assembly Line.,Meinke JL, Mehaffey MR, Wagner DT, Sun N, Zhang Z, Brodbelt JS, Keatinge-Clay AT ACS Chem Biol. 2018 Nov 9. doi: 10.1021/acschembio.8b00733. PMID:30371052^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.