Title | Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | McCoy JG, Johnson HD, Singh S, Bingman CA, Lei I-K, Thorson JS, Phillips GN |
Journal | Proteins |
Volume | 74 |
Issue | 1 |
Pagination | 50-60 |
Date Published | 2009 Jan |
ISSN | 1097-0134 |
Keywords | Acyl Carrier Protein, Animals, Bacterial Proteins, Biosynthetic Pathways, Coenzyme A, Crystallography, X-Ray, Escherichia coli, Iodine, Ligands, Micromonospora, Oxidoreductases, Polyketide Synthases, Protein Binding, Protein Structure, Tertiary, Resorcinols, Streptomyces |
Abstract | Although bacterial iterative Type I polyketide synthases are now known to participate in the biosynthesis of a small set of diverse natural products, the subsequent downstream modification of the resulting polyketide products remains poorly understood. Toward this goal, we report the X-ray structure determination at 2.5 A resolution and preliminary characterization of the putative orsellenic acid P450 oxidase (CalO2) involved in calicheamicin biosynthesis. These studies represent the first crystal structure for a P450 involved in modifying a bacterial iterative Type I polyketide product and suggest the CalO2-catalyzed step may occur after CalO3-catalyzed iodination and may also require a coenzyme A- (CoA) or acyl carrier protein- (ACP) bound substrate. Docking studies also reveal a putative docking site within CalO2 for the CLM orsellinic acid synthase (CalO5) ACP domain which involves a well-ordered helix along the CalO2 active site cavity that is unique compared with other P450 structures. |
DOI | 10.1002/prot.22131 |
Alternate Journal | Proteins |
PubMed ID | 18561189 |
PubMed Central ID | PMC2742692 |
Grant List | 5T32HG002760 / HG / NHGRI NIH HHS / United States CA84374 / CA / NCI NIH HHS / United States PSO GM64598 / GM / NIGMS NIH HHS / United States R01 CA084374 / CA / NCI NIH HHS / United States R01 CA084374-10 / CA / NCI NIH HHS / United States T32-GM008505 / GM / NIGMS NIH HHS / United States U19 CA113297 / CA / NCI NIH HHS / United States Y1-CO-1020 / CO / NCI NIH HHS / United States Y1-GM-1104 / GM / NIGMS NIH HHS / United States |