Identification of Mycobacterium tuberculosis enzyme involved in vitamin D and 7-dehydrocholesterol metabolism.
Problems arising during treatment of tuberculosis are well known, therefore studies of Mycobacterium drug molecular targets are an area of particular importance. Members of the cytochrome P450 family (CYP) may belong to potential candidates for drug targets being involved in metabolism of biologically important molecules in the host organism. CYP124 of Mycobacterium tuberculosis (MTCYP124) catalyzes ω-hydroxylation of methyl-branched lipids. The data obtained in the present study indicate that this enzyme can also oxidize provitamin D3 (7-dehydrocholesterol) and vitamin D3. We found that the final product is different from 1α- and 25-hydroxyvitamin D3, so we propose that MTCYP124 is involved in alternative pathway for metabolism of vitamin D3.
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus.
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Vasilevskaya
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus.
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Yantsevich
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus.
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Sergeev
Institute of an Experimental Veterinary Science n. S.N. Wyshelesski, 220003, Minsk, Briketa 28, Belarus.
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Lemish
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus.
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Usanov
Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus. Electronic address: agilep@iboch.bas-net.by.
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Gilep
D001426:Bacterial Proteins / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D002762:Cholecalciferol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003684:Dehydrocholesterols / Q000378:metabolism*; D008024:Ligands; D013058:Mass Spectrometry; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D003684:Dehydrocholesterols; D008024:Ligands; D002762:Cholecalciferol; D003577:Cytochrome P-450 Enzyme System; C016705:7-dehydrocholesterol
7-Dehydrocholesterol; Cytochrome P450; Steroid metabolism; Vitamin D