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dc.contributor.author Sherman, David H.
dc.contributor.author Lamb, David C.
dc.contributor.author Podust, Larissa M.
dc.contributor.author Bach, Horacio
dc.contributor.author Waterman, Michael R.
dc.contributor.author Kim, Youngchang
dc.contributor.author Kelly, Steven L.
dc.contributor.author Arase, Miharu
dc.date.accessioned 2009-09-09T08:38:42Z
dc.date.available 2009-09-09T08:38:42Z
dc.date.issued 2004
dc.identifier.citation Sherman , D H , Lamb , D C , Podust , L M , Bach , H , Waterman , M R , Kim , Y , Kelly , S L & Arase , M 2004 , ' Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways ' Science , pp. 255-268 . , 10.1110/ps.03384804 en
dc.identifier.issn 1095-9203
dc.identifier.other PURE: 123903
dc.identifier.other dspace: 2160/3018
dc.identifier.uri http://hdl.handle.net/2160/3018
dc.description Podust, L. M., Bach, H., Kim, Y., Lamb, D. C., Arase, M., Sherman, D. H., Kelly, S. L., Waterman, M. R. (2004). Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways.  Protein Science, 13, (1), 255-268 Sponsorship: This work was supported by NIH grants GM37942 and ES00267 (to M.R.W.), P30 ES00267 (to L.M.P.), GM48562 (to D.H.S.), as well as by Biotechnology and Biological Sciences Research Council (to S.L.K. and D.C.L.) and a Wellcome Trust grant (to D.C.L. and M.R.W.). en
dc.description.abstract The genus Streptomyces produces two-thirds of microbially derived antibiotics. Polyketides form the largest and most diverse group of these natural products. Antibiotic diversity of polyketides is generated during their biosynthesis by several means, including postpolyketide modification performed by oxidoreductases, a broad group of enzymes including cytochrome P450 monooxygenases (CYPs). CYPs catalyze site-specific oxidation of macrolide antibiotic precursors significantly affecting antibiotic activity. Efficient manipulation of Streptomyces CYPs in generating new antibiotics will require identification and/or engineering of monooxygenases with activities toward a diverse array of chemical substrates. To begin to link structure to function of CYPs involved in secondary metabolic pathways of industrially important species, we determined the X-ray structure of Streptomyces coelicolor A3(2) CYP154A1 at 1.85 Å and analyzed it in the context of the closely related CYP154C1 and more distant CYPs from polyketide synthase (EryF) and nonribosomal peptide synthetase (OxyB) biosynthetic pathways. In contrast to CYP154C1, CYP154A1 reveals an active site inaccessible from the molecular surface, and an absence of catalytic activities observed for CYP154C1. Systematic variations in the amino acid patterns and length of the surface HI loop correlate with degree of rotation of the F and G helices relative to the active site in CYP154A1-related CYPs, presumably regulating the degree of active site accessibility and its dimensions. Heme in CYP154A1 is in a 180° flipped orientation compared with most other structurally determined CYPs. en
dc.format.extent 14 en
dc.language.iso eng
dc.relation.ispartof Science en
dc.title Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1110/ps.03384804
dc.contributor.institution Aberystwyth University en
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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