title: Purine Salvage Pathway in Mycobacterium tuberculosis.
abstract: Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: R G
authors.initials: RG
authors.lastname: Ducati
authors.forename: A
authors.initials: A
authors.lastname: Breda
authors.forename: L A
authors.initials: LA
authors.lastname: Basso
authors.forename: D S
authors.initials: DS
authors.lastname: Santos
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000264:Adenylosuccinate Lyase / Q000378:metabolism; D000265:Adenylosuccinate Synthase / Q000378:metabolism; D007168:IMP Dehydrogenase / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D011687:Purines / Q000378:metabolism*
chemical_list: D011687:Purines; D007168:IMP Dehydrogenase; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D000248:Adenosine Kinase; D009703:Nucleoside-Phosphate Kinase; D015720:5'-Nucleotidase; D009699:N-Glycosyl Hydrolases; C030681:purine nucleosidase; D000243:Adenosine Deaminase; D000264:Adenylosuccinate Lyase; D000265:Adenylosuccinate Synthase; C030985:purine