4x7w

MycF mycinamicin III 3'-O-methyltransferase (E35Q, E139A variant) in complex with Mg, SAH and mycinamicin VI (MycE substrate)

spinqualitylabelsall models 4x7w, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4x7w is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, MVI, SAH Related: 4x7v, 4x7z, 4x7y, 4x81, 4x7x, 4x7u Activity: -O-methyltransferase Mycinamicin III 3-O-methyltransferase, with EC number 2.1.1.237 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MYCF_MICGR] O-methyltransferase that catalyzes the conversion of mycinamicin III to mycinamicin IV in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. Publication Abstract from PubMed Sugar moieties in natural products are frequently modified by O-methylation. In the biosynthesis of the macrolide antibiotic mycinamicin, methylation of a 6'-deoxyallose substituent occurs in a stepwise manner first at the 2'- and then the 3'-hydroxyl groups to produce the mycinose moiety in the final product. The timing and placement of the O-methylations impact final stage C-H functionalization reactions mediated by the P450 monooxygenase MycG. The structural basis of pathway ordering and substrate specificity is unknown. A series of crystal structures of MycF, the 3'-O-methyltransferase, including the free enzyme and complexes with S-adenosyl homocysteine (SAH), substrate, product, and unnatural substrates, show that SAM binding induces substantial ordering that creates the binding site for the natural substrate, and a bound metal ion positions the substrate for catalysis. A single amino acid substitution relaxed the 2'-methoxy specificity but retained regiospecificity. The engineered variant produced a new mycinamicin analog, demonstrating the utility of structural information to facilitate bioengineering approaches for the chemoenzymatic synthesis of complex small molecules containing modified sugars. Using the MycF substrate complex and the modeled substrate complex of a 4'-specific homologue, active site residues were identified that correlate with the 3' or 4' specificity of MycF family members and define the protein and substrate features that direct the regiochemistry of methyltransfer. This classification scheme will be useful in the annotation of new secondary metabolite pathways that utilize this family of enzymes. Structural Basis of Substrate Specificity and Regiochemistry in the MycF/TylF Family of Sugar O-Methyltransferases.,Bernard SM, Akey DL, Tripathi A, Park SR, Konwerski JR, Anzai Y, Li S, Kato F, Sherman DH, Smith JL ACS Chem Biol. 2015 Feb 26. PMID:25692963 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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