Objetivo
Mycobacterium tuberculosis (Mtb) is the biggest killer among infectious diseases. Multi-drug resistant strains are widespread. New antibiotic strategies are desperately needed to combat the deadly pathogen. The genome sequence of Mtb revealed that Mtb encodes a high number (~20) of cytochromes P450 (P450s). These enzymes have roles in sterol, lipid and and polyketide metabolism in the cell. The recent determination of the genome sequence of the leprosy pathogen (M. leprae) indicates a much smaller number of proteins encoded, with only a single P450 remaining. The remaining P450 is likely to be essential for bacterial viability. Azole drugs which inhibit activity of P450 enzymes also exhibit potent anti-mycobacterial effects. This suggests that azoles may be useful new drugs against these deadly pathogens. The major objectives of this proposal are the systematic study of the sole M. leprae P450 and its homologue in M. tuberculosis. This will involve protein expression and purification of the P450s, and detailed kinetic, spectroscopic and structural analysis of these enzymes. The substrate selectivity will be determined by spectral titrations and lipid analysis, and activity will be reconstituted with expressed redox partners. Azoles interactions will be also be examined. Collectively, these studies will allow fundamental understanding of these P450s' properties and their potential as drug targets.
Ámbito científico (EuroSciVoc)
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
- ciencias médicas y de la saludciencias de la saludenfermedad infecciosa
- ciencias naturalesciencias biológicasbioquímicabiomoléculaslípidos
- ciencias médicas y de la saludmedicina básicafarmacología y farmaciafarmacorresistenciaresistencia a múltiple fármacos
- ciencias naturalesciencias biológicasgenéticagenoma
- ciencias naturalesciencias biológicasbioquímicabiomoléculasproteínasenzima
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Tema(s)
Data not availableConvocatoria de propuestas
Data not availableRégimen de financiación
RGI - Research grants (individual fellowships)Coordinador
LE1 7RH LEICESTER
Reino Unido