1GWI

The 1.92 A structure of Streptomyces coelicolor A3(2) CYP154C1: A new monooxygenase that functionalizes macrolide ring systems

Summary for 1GWI

• Entry DOI: 10.2210/pdb1gwi/pdb
• Descriptor: CYTOCHROME P450 154C1, SULFATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• Functional Keywords: oxidoreductase, streptomyces, cyp154c1, macrolide antibiotics, 12- and 14- carbon macrolactone monooxygenase, heme, oxidoreductase.
• Biological source: STREPTOMYCES COELICOLOR
• Total number of polymer chains: 2
• Total formula weight: 90960.65

Authors

Podust, L.M.,Kim, Y.,Arase, M.,Neely, B.A.,Beck, B.J.,Bach, H.,Sherman, D.H.,Lamb, D.C.,Kelly, S.L.,Waterman, M.R. (deposition date: 2002-03-15, release date: 2003-01-29, Last modification date: 2024-05-08)

Primary citation

Podust, L.M.,Kim, Y.,Arase, M.,Neely, B.A.,Beck, B.J.,Bach, H.,Sherman, D.H.,Lamb, D.C.,Kelly, S.L.,Waterman, M.R.
The 1.92 A Structure of Streptomyces Coelicolor A3(2) Cyp154C1: A New Monooxygenase that Functionalizes Macrolide Ring Systems
J.Biol.Chem., 278:12214-, 2003

PubMed Abstract: 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.

PubMed: 12519772
DOI: 10.1074/JBC.M212210200

Experimental method

X-RAY DIFFRACTION (1.92 Å)