1gwi

From Proteopedia

Revision as of 13:32, 18 December 2007

THE 1.92 A STRUCTURE OF STREPTOMYCES COELICOLOR A3(2) CYP154C1: A NEW MONOOXYGENASE THAT FUNCTIONALIZES MACROLIDE RING SYSTEMS

Overview

Evolutionary links between cytochrome P450 monooxygenases, a superfamily, of extraordinarily divergent heme-thiolate proteins catalyzing a wide, array of NADPH/NADH- and O(2)-dependent reactions, are becoming better, understood because of availability of an increasing number of fully, sequenced genomes. Among other reactions, P450s catalyze the site-specific, oxidation of the precursors to macrolide antibiotics in the genus, Streptomyces introducing regiochemical diversity into the macrolide ring, system, thereby significantly increasing antibiotic activity. Developing, effective uses for Streptomyces enzymes in biosynthetic processes and, bioremediation requires identification and engineering of additional, monooxygenases with activities toward a diverse array of small molecules., To elucidate the molecular basis for substrate specificity of oxidative, enzymes toward macrolide antibiotics, the x-ray structure of CYP154C1 from, Streptomyces coelicolor A3(2) was determined (Protein Data Bank code )., Relocation of certain common P450 secondary structure elements, along with, a novel structural feature involving an additional beta-strand, transforming the five-stranded beta-sheet into a six-stranded variant, creates an open cleft-shaped substrate-binding site between the two P450, domains. High sequence similarity to macrolide monooxygenases from other, microbial species translates into catalytic activity of CYP154C1 toward, both 12- and 14-membered ring macrolactones in vitro.

About this Structure

1GWI is a Single protein structure of sequence from Streptomyces coelicolor with SO4 and HEM as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The 1.92-A structure of Streptomyces coelicolor A3(2) CYP154C1. A new monooxygenase that functionalizes macrolide ring systems., Podust LM, Kim Y, Arase M, Neely BA, Beck BJ, Bach H, Sherman DH, Lamb DC, Kelly SL, Waterman MR, J Biol Chem. 2003 Apr 4;278(14):12214-21. Epub 2003 Jan 7. PMID:12519772

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