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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.3
- 수록면
- 211 - 216 (6page)
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CYP107W1 from Streptomyces avermitilis is a cytochrome P450 enzyme involved in the biosynthesis of macrolide oligomycin A. A previous study reported that CYP107W1 regioselectively hydroxylated C12 of oligomycin C to produce oligomycin A, and the crystal structure of ligand free CYP107W1 was determined. Here, we analyzed the structural properties of the CYP107W1-oligomycin A complex and characterized the functional role of the Trp178 residue in CYP107W1. The crystal structure of the CYP107W1 complex with oligomycin A was determined at a resolution of 2.6 A. Oligomycin A is bound in the substrate access channel on the upper side of the prosthetic heme mainly by hydrophobic interactions. In particular, the Trp178 residue in the active site intercalates into the large macrolide ring, thereby guiding the substrate into the correct binding orientation for a productive P450 reaction. A Trp178 to Gly mutation resulted in the distortion of binding titration spectra with oligomycin A, whereas binding spectra with azoles were not affected. The Gly178 mutant’s catalytic turnover number for the 12-hydroxylation reaction of oligomycin C was highly reduced. These results indicate that Trp178, located in the open pocket of the active site, may be a critical residue for the productive binding conformation of large macrolide substrates.
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참고문헌 (22)
참고문헌 신청
Burg, R. W. / 1979 / Avermectins, new family of potent anthelmintic agents : producing organism and fermentation / Antimicrob. Agents Chemother 15:361~367
최승혜 / 2013 / Evaluation of Luminescent P450 Analysis for Directed Evolution of Human CYP4A11 / Biomolecules & Therapeutics 21(6):487~492
Durairaj, P. / 2015 / Fungal cytochrome P450monooxygenases of Fusarium oxysporum for the synthesis of omega-hydroxy fatty acids in engineered Saccharomyces cerevisiae / Microb Cell Fact 14:45
Dyson, P. / 2011 / Streptomyces : Molecular Biology and Biotechnology / Caister Academic Press
Emsley, P. / 2004 / Coot : model-building tools for molecular graphics / Acta Crystallogr. D. Biol. Crystallogr 60:2126~2132
최승혜 / 2013 / Evaluation of Luminescent P450 Analysis for Directed Evolution of Human CYP4A11 / Biomolecules & Therapeutics 21(6):487~492
Durairaj, P. / 2015 / Fungal cytochrome P450monooxygenases of Fusarium oxysporum for the synthesis of omega-hydroxy fatty acids in engineered Saccharomyces cerevisiae / Microb Cell Fact 14:45
Dyson, P. / 2011 / Streptomyces : Molecular Biology and Biotechnology / Caister Academic Press
Emsley, P. / 2004 / Coot : model-building tools for molecular graphics / Acta Crystallogr. D. Biol. Crystallogr 60:2126~2132
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