Cytochromes p450 as drug targets against mycobacterium tuberculosis and mycobacterium leprae.

Informations projet

N° de convention de subvention: HPMF-CT-2002-01633

Projet clôturé

Date de début 1 Avril 2002

Date de fin 31 Mars 2004

Financé au titre de

• Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Coût total € 114 072,00

Contribution de l’UE € 114 072,00

Coordonné par

UNIVERSITY OF LEICESTER
United Kingdom

Objectif

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.

Champ scientifique (EuroSciVoc)

CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.

• sciences médicales et de la santé › sciences de la santé › maladie infectieuse
• sciences naturelles › sciences biologiques › biochimie › biomolécule › lipides
• sciences médicales et de la santé › médecine fondamentale › pharmacologie et pharmacie › résistance aux médicaments › résistance multiple aux médicaments
• sciences naturelles › sciences biologiques › génétique › génome
• sciences naturelles › sciences biologiques › biochimie › biomolécule › protéines › enzyme

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Programme(s)

• FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Thème(s)

Data not available

Appel à propositions

Data not available

Régime de financement

RGI - Research grants (individual fellowships)

Coordinateur

UNIVERSITY OF LEICESTER

• Contribution de l’UE: Aucune donnée
• Adresse: The Adrian Building, University Road ; LE1 7RH LEICESTER ; Royaume-Uni
• Coût total: Aucune donnée