1s1f
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Crystal Structure of Streptomyces Coelicolor A3(2) CYP158A2 from antibiotic biosynthetic pathways
OverviewOverview
Cytochrome P450 158A2 (CYP158A2) is encoded within a three-gene operon, (sco1206-sco1208) in the prototypic soil bacterium Streptomyces coelicolor, A3(2). This operon is widely conserved among streptomycetes. CYP158A2 has, been suggested to produce polymers of flaviolin, a pigment that may, protect microbes from UV radiation, in combination with the adjacent rppA, gene, which encodes the type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase. Following cloning, expression, and purification of this cytochrome P450, we have shown that it can, produce dimer and trimer products from the substrate flaviolin and that, the structures of two of the dimeric products were established using mass, spectrometry and multiple NMR methods. A comparison of the x-ray, structures of ligand-free (1.75 angstroms) and flaviolin-bound (1.62, angstroms) forms of CYP158A2 demonstrates a major conformational change, upon ligand binding that closes the entry into the active site, partly due, to repositioning of the F and G helices. Particularly interesting is the, presence of two molecules of flaviolin in the closed active site. The, flaviolin molecules form a quasi-planar three-molecule stack including the, heme of CYP158A2, suggesting that oxidative C-C coupling of these phenolic, molecules leads to the production of flaviolin dimers.
About this StructureAbout this Structure
1S1F is a Single protein structure of sequence from Bacteria with HG, HEM, PIM, MLA and GOL as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2., Zhao B, Guengerich FP, Bellamine A, Lamb DC, Izumikawa M, Lei L, Podust LM, Sundaramoorthy M, Kalaitzis JA, Reddy LM, Kelly SL, Moore BS, Stec D, Voehler M, Falck JR, Shimada T, Waterman MR, J Biol Chem. 2005 Mar 25;280(12):11599-607. Epub 2005 Jan 19. PMID:15659395
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