Full text
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| Author(s): |
Márcio Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Carlos. |
| Institution: | Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) |
| Defense date: | 2005-06-03 |
| Examining board members: |
Otavio Henrique Thiemann;
Fabio Ceneviva Lacerda de Almeida;
Luis Fernando Delboni;
Javier Alcides Ellena;
Francisco Javier Medrano Martin
|
| Advisor: | Otavio Henrique Thiemann; Glaucius Oliva |
| Abstract | |
This thesis in its introduction presents a brief bibliografic revision about the importance of the phosphoribosyltransferase enzyme (PRTases) to cellular homeostasis, both in mammalian cell as in the protozoa Kinetoplastida. It is emphasized the close relation between point mutatons found in the gene coding for Adenine phosphoribosyltransferase (APRT) and disease Dihidroxiadenine Urolitiasis. The deseases leishmaniasis, caused by Kinetoplastidae beloing to the Leishmania genera, is described indicating the possible use of the purine salvage pathway (PRTases) as targets for the future development of novel drugs against leishmaniasis. The experience described in this thesis aims at the heterologous production of the enzyme APRT of Homo sapiens, its crystallographic structure elucidation and structural analysis of mutations found in patient with Dihidroxiadenine Urolitiasis. The Leishmania tarentolae homologue was also the aim of this work. With this APRT the experiments describes in this thesis aim at the structural resolution of the enzyme and its use in the screening for novel PRTases inhibitors. The results presented in this thesis show that the objectives of the work have been achieved. The structural elucidation of the human APRT allowed the discussion of the potential modifications caused bu the point mutations in the APRT gene. Novel inhibitors of PRTases of Leishmania major promastigote cultures and promoted the growth inhibition of this parasite. (AU) | |