title: Pyrimidine salvage pathway in Mycobacterium tuberculosis.
abstract: The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: A D
authors.initials: AD
authors.lastname: Villela
authors.forename: Z A
authors.initials: ZA
authors.lastname: Sánchez-Quitian
authors.forename: R G
authors.initials: RG
authors.lastname: Ducati
authors.forename: D S
authors.initials: DS
authors.lastname: Santos
authors.forename: L A
authors.initials: LA
authors.lastname: Basso
mesh_terms: D003564:Cytidine Deaminase / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D009709:Nucleotide Deaminases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D057845:Pyrimidine Phosphorylases / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D011743:Pyrimidines; D013940:Thymidylate Synthase; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; C023269:uracil phosphoribosyltransferase; D009703:Nucleoside-Phosphate Kinase; D009701:Nucleoside-Diphosphate Kinase; D009709:Nucleotide Deaminases; C019988:dCTP deaminase; D003564:Cytidine Deaminase; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; C030986:pyrimidine