1odo: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==Overview== | ||
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 ... | 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 A 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, degrees flipped orientation compared with most other structurally, determined CYPs. | ||
==About this Structure== | ==About this Structure== | ||
1ODO is a | 1ODO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor] with HEM and PIM as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ODO OCA]. | ||
==Reference== | ==Reference== | ||
| Line 29: | Line 29: | ||
[[Category: streptomyces]] | [[Category: streptomyces]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:49:29 2007'' | ||
Revision as of 15:44, 5 November 2007
|
1.85 A STRUCTURE OF CYP154A1 FROM STREPTOMYCES COELICOLOR A3(2)
OverviewOverview
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 A 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, degrees flipped orientation compared with most other structurally, determined CYPs.
About this StructureAbout this Structure
1ODO is a Single protein structure of sequence from Streptomyces coelicolor with HEM and PIM as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
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., Podust LM, Bach H, Kim Y, Lamb DC, Arase M, Sherman DH, Kelly SL, Waterman MR, Protein Sci. 2004 Jan;13(1):255-68. PMID:14691240
Page seeded by OCA on Mon Nov 5 14:49:29 2007