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Previous issue date: 2014-08-22 / Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. The increasing number of infected patients among immune compromised populations and emergence of drug-resistant strains has created urgent need of new strategies to treat TB. Understanding relevant pathways (as the purine salvage) will reveal details of M. tuberculosis that might be used to develop new strategies to combat this pathogen. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme from the purine phosphoribosyltransferase (PRTase) family and catalyzes the conversion of hypoxanthine or guanine and 5-phosphoribosyl-α-1-pyrophosphate (PRPP) to inosine 5 -monophosphate (IMP) or guanosine 5 -monophosphate (GMP), and pyrophosphate (PPi). Here we describe the mode of action of M. tuberculosis HGPRT (MtHGPRT) through kinetic and thermodynamical analysis. Experiments were also performed to determine the oligomeric state in solution, pH, temperature and solvent isotope effects. These data allows us to compare MtHGPRT to homologues from other species and look for similarities and differences in its mechanism and constants. We hope the experiments presented here will contribute to the understanding of this pathogen purine salvage pathway. / A Tuberculose (TB) ? uma doen?a infecciosa causada principalmente por Mycobacterium tuberculosis. O aumento de pacientes infectados entre a popula??o imunocomprometida e a emerg?ncia de cepas resistentes a drogas criam uma necessidade de novas estrat?gias para tartar a TB. Entender como funcionam as vias metab?licas relevantes, como a via de salvamento de purinas, poder? revelar detalhes do M. tuberculosis que poder?o ser ?teis para o desenvolvimento de novas estrat?gias de combate a este pat?geno. A hipoxantina-guanina fosforribosiltransferase (HGPRT) ? uma enzima da familia das purina fosforribosiltransferases (PRTase) e catalisa a convers?o de hipoxantina ou guanina e 5-fosforribosilpirofosfato-α-1-pirofosfato (PRPP) em inosina 5 -monofosfato (IMP) ou guanosina 5 -monofosfato (GMP) respectivamente, com a libera??o de pirofosfato inorg?nico (PPi). Aqui n?s descrevemos o modo de a??o da HGPRT de M. tuberculosis (MtHGPRT) atrav?s de an?lises cin?ticas e termodin?micas. Tamb?m foram realizados experimentos para determinar o estado oligom?rico da enzima em solu??o e os efeitos de pH, temperatura e efeitos isot?picos do solvente. Esses dados nos permitem comparar a MtHGPRT com hom?logos de outras esp?cies e procurar por similaridades e diferen?as nos seu mecanismo e constantes. N?s esperamos que os experimentos apresentados aqui contribuam para o entendimento da via de salvamento de purinas desse pat?geno.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/5509 |
| Date | 22 August 2014 |
| Creators | Patta, Paulo Cesar |
| Contributors | Basso, Luiz Augusto |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biologia Celular e Molecular, PUCRS, BR, Faculdade de Bioci?ncias |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Unknown |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 8198246930096637360, 600, 600, 36528317262667714 |
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