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

Project Information

Grant agreement ID: HPMF-CT-2002-01633

Project closed

Start date 1 April 2002

End date 31 March 2004

Funded under

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

Total cost € 114 072,00

EU contribution € 114 072,00

Coordinated by

UNIVERSITY OF LEICESTER
United Kingdom

Objective

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.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.

• medical and health sciences › health sciences › infectious diseases
• natural sciences › biological sciences › biochemistry › biomolecules › lipids
• medical and health sciences › basic medicine › pharmacology and pharmacy › drug resistance › multidrug resistance
• natural sciences › biological sciences › genetics › genomes
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

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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)

Topic(s)

Data not available

Call for proposal

Data not available

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

UNIVERSITY OF LEICESTER

• EU contribution: No data
• Address: The Adrian Building, University Road ; LE1 7RH LEICESTER ; United Kingdom
• Total cost: No data