5foi

Crystal structure of mycinamicin VIII C21 methyl hydroxylase MycCI from Micromonospora griseorubida bound to mycinamicin VIII

spinqualitylabelsall models 5foi, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5foi is a 2 chain structure with sequence from Micromonospora griseorubida. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: GOL, HEM, MY8, SPD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYCCI_MICGR Involved in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. Catalyzes hydroxylation at the C21 methyl group of mycinamicin VIII, the earliest macrolide form in the postpolyketide synthase tailoring pathway, leading to mycinamicin VII. Uses ferredoxin MycCII in electron transfer for catalysis. Publication Abstract from PubMed Cytochrome P450 monooxygenases (P450s) are some of nature's most ubiquitous and versatile enzymes for performing oxidative metabolic transformations. Their unmatched ability to selectively functionalize inert C-H bonds has led to their increasing employment in academic and industrial settings for the production of fine and commodity chemicals. Many of the most interesting and potentially biocatalytically useful P450s come from microorganisms, where they catalyze key tailoring reactions in natural product biosynthetic pathways. While most of these enzymes act on structurally complex pathway intermediates with high selectivity, they often exhibit narrow substrate scope, thus limiting their broader application. In the present study, we investigated the reactivity of the P450 MycCI from the mycinamicin biosynthetic pathway toward a variety of macrocyclic compounds and discovered that the enzyme exhibits appreciable activity on several 16-membered ring macrolactones independent of their glycosylation state. These results were corroborated by performing equilibrium substrate binding experiments, steady-state kinetics studies, and x-ray crystallographic analysis of MycCI bound to its native substrate mycinamicin VIII. We also characterized TylHI, a homologous P450 from the tylosin pathway, and showed that its substrate scope is severely restricted compared to MycCI. Thus, the ability of the latter to hydroxylate both macrocyclic aglycones and macrolides sets it apart from related biosynthetic P450s and highlights its potential for developing novel P450 biocatalysts with broad substrate scope and high regioselectivity. Biochemical and Structural Characterization of MycCI, a Versatile P450 Biocatalyst from the Mycinamicin Biosynthetic Pathway.,DeMars MD, Sheng F, Park SR, Lowell AN, Podust LM, Sherman DH ACS Chem Biol. 2016 Jul 15. PMID:27420774 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA