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Previous issue date: 2014-03-31 / Tuberculosis (TB), a disease mainly caused by the bacillus Mycobacterium tuberculosis (MTB), is considered a global public health problem. Infections caused by mycobacteria are generally difficult to treat because of its natural resistance to most antibiotics. This resistance is largely attributed to the formation of the cell wall. The InhA is part of the mycobacterial FAS II system which regulates the elongation of the fatty acid chain, which will compose the cell wall of the bacillus (mycolic acids). As the FAS II system is not present in mammals, this enzyme has been described as an important macromolecular target aiming the development of drugs with selective toxicity. The development of analytical techniques for studying proteins in solution by mass spectrometry combined with cross-linking has permitted access information about the primary, tertiary, and quaternary structure of the proteins. In this work, the technique of cross-linking combined with mass spectrometry was implemented for the characterization of the Mycobacterium tuberculosis enoyl-ACP reductase (InhA) which catalyzes the final essential enzymatic step in fatty acid elongation in the FAS II pathway, converting 2-trans-enoyl-ACP to acyl-ACP via an NADH-dependent reaction. / A tuberculose (TB), doen?a causada principalmente pelo bacilo Mycobacterium tuberculosis (MTB), ? considerada um problema global de sa?de p?blica. As infec??es causadas pela micobact?ria s?o, em geral, dif?ceis de tratar devido principalmente ao surgimento de cepas resistentes ? maioria dos f?rmacos dispon?veis e ? co-infec??o com a s?ndrome da imunodefici?nciaadquirida (SIDA). Nesse contexto, a caracteriza??o de alvos moleculares para a proposi??o de novas estruturas qu?micas candidatas a f?rmacos anti-TB mostra-se de import?ncia sum?ria. A enzima enoil-ACP-redutase (InhA) de MTB faz parte do sistema FAS II damicobact?ria a qual regula o alongamento da cadeia dos ?cidos graxos fornecendo os precursores que ir?o compor a parede celular do bacilo (?cidos mic?licos). Como o sistema FAS II n?o esta presente em mam?feros esse fato torna essa enzima um importante alvo macromolecular para o desenvolvimento de novos f?rmacos com toxicidade seletiva. O desenvolvimento de t?cnicas anal?ticas para estudar prote?nas em solu??o utilizando a espectrometria de massas combinada com agentes de liga??o cruzada vem possibilitandoa caracteriza??o estrutural de prote?nas conduzindo a informa??es sobre suas estruturas prim?rias, terci?rias e quatern?rias. No presente trabalho foi implementado a t?cnica de cross-linking combinada a espectrometria de massas para a caracteriza??o em solu??o da enzima InhA de MTB.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/5510 |
| Date | 31 March 2014 |
| Creators | Santos, Anderson Jader Antunes Brizola dos |
| Contributors | Machado, Pablo |
| 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 | English |
| 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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