2yca

Mixed-function P450 MycG in complex with mycinamicin III in P21212 space group

spinqualitylabelsall models 2yca, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yca is a 1 chain structure with sequence from 'micromonospora griseorubida'. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, HEM, SIN, ZM3 Related: 2y5n, 2y46, 2y5z, 2y98 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The majority of characterized cytochrome P450 enzymes in actinomycete secondary metabolic pathways are strictly substrate-, regio- and stereo-specific. Examples of multifunctional biosynthetic cytochromes P450 with broader substrate and regio-specificity are growing in number and are of particular interest for biosynthetic and chemoenzymatic applications. MycG is among the first P450 monooxygenases characterized that catalyzes both hydroxylation and epoxidation reactions in the final biosynthetic steps, leading to oxidative tailoring of the 16-membered ring macrolide antibiotic mycinamicin II (M-II) in the actinomycete Micromonospora griseorubida. The ordering of steps to complete the biosynthetic process involves a complex substrate recognition pattern by the enzyme and interplay between three tailoring modifications: glycosylation, methylation and oxidation. To understand the catalytic properties of MycG, we structurally characterized the ligand-free enzyme and its complexes with three native metabolites. These include substrates mycinamicin IV (M-IV) and V (M-V), and their biosynthetic precursor mycinamicin III (M-III), which carries the monomethoxy sugar javose instead of the dimethoxylated sugar mycinose. The two methoxy groups of mycinose serve as sensors that mediate initial recognition to discriminate between closely related substrates in the post-polyketide oxidative tailoring of mycinamycin metabolites. Since x-ray structures alone did not explain the mechanisms of macrolide hydroxylation and epoxidation, paramagnetic NMR relaxation measurements were conducted. Molecular modeling based on these data indicates that in solution substrate may penetrate the active site sufficiently to place the abstracted hydrogen atom of M-IV within 6 A of the heme iron, and ~4 A of the oxygen of Fe-ligated water. Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions.,Li S, Tietz DR, Rutaganira FU, Kells PM, Anzai Y, Kato F, Pochapsky TC, Sherman DH, Podust LM J Biol Chem. 2012 Sep 5. PMID:22952225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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