3sso
From Proteopedia
MycE Methyltransferase from the Mycinamycin Biosynthetic Pathway in Complex with Mg and SAH, Crystal form 2
Structural highlights
Function[MYCE_MICGR] O-methyltransferase that catalyzes the conversion of mycinamicin VI to mycinamicin III in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic.[1] [2] Publication Abstract from PubMedO-linked methylation of sugar substituents is a common modification in the biosynthesis of many natural products and is catalyzed by multiple families of S-adenosyl-L-methionine (SAM or AdoMet)-dependent methyltransferases (MTs). Mycinamicins, potent antibiotics from Micromonospora griseorubida, can be methylated at two positions on a 6-deoxyallose substituent. The first methylation is catalyzed by MycE, a SAM- and metal-dependent MT. Crystal structures were determined for MycE bound to the product S-adenosyl-L-homocysteine (AdoHcy) and magnesium, both with and without the natural substrate mycinamicin VI. This represents the first structure of a natural product sugar MT in complex with its natural substrate. MycE is a tetramer of a two-domain polypeptide, comprising a C-terminal catalytic MT domain and an N-terminal auxiliary domain, which is important for quaternary assembly and for substrate binding. The symmetric MycE tetramer has a novel MT organization in which each of the four active sites is formed at the junction of three monomers within the tetramer. The active-site structure supports a mechanism in which a conserved histidine acts as a general base, and the metal ion helps to position the methyl acceptor and to stabilize a hydroxylate intermediate. A conserved tyrosine is suggested to support activity through interactions with the transferred methyl group from the SAM methyl donor. The structure of the free enzyme reveals a dramatic order-disorder transition in the active site relative to the S-adenosyl-L-homocysteine complexes, suggesting a mechanism for product/substrate exchange through concerted movement of five loops and the polypeptide C-terminus. A new structural form in the SAM/metal-dependent omethyltransferase family: MycE from the mycinamicin biosynthetic pathway.,Akey DL, Li S, Konwerski JR, Confer LA, Bernard SM, Anzai Y, Kato F, Sherman DH, Smith JL J Mol Biol. 2011 Oct 21;413(2):438-50. Epub 2011 Aug 23. PMID:21884704[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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