publication . Article . Other literature type . 2009

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis.

Belin, P.; Le Du, Marie-Hélène; Fielding, A.; Lequin, O.; Jacquet, M.; Charbonnier, Jean-Baptiste; Lecoq, A.; Thai, Robert; Courcon, M.; Masson, C.; ...
Open Access English
  • Published: 05 May 2009
  • Publisher: HAL CCSD
  • Country: France
Abstract
International audience; The gene encoding the cytochrome P450 CYP121 is essential for Mycobacterium tuberculosis. However, the CYP121 catalytic activity remains unknown. Here, we show that the cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) binds to CYP121, and is efficiently converted into a single major product in a CYP121 activity assay containing spinach ferredoxin and ferredoxin reductase. NMR spectroscopy analysis of the reaction product shows that CYP121 catalyzes the formation of an intramolecular C-C bond between 2 tyrosyl carbon atoms of cYY resulting in a novel chemical entity. The X-ray structure of cYY-bound CYP121, solved at high resolution (1.4 A), reveal...
Subjects
free text keywords: [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biological Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multidisciplinary, Heme, chemistry.chemical_compound, chemistry, Ligand, Rational design, Intramolecular force, Ferredoxin, Active site, biology.protein, biology, Nuclear magnetic resonance spectroscopy, Stereochemistry, Protein structure
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publication . Article . Other literature type . 2009

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis.

Belin, P.; Le Du, Marie-Hélène; Fielding, A.; Lequin, O.; Jacquet, M.; Charbonnier, Jean-Baptiste; Lecoq, A.; Thai, Robert; Courcon, M.; Masson, C.; ...