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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-22022016-153037
Document
Author
Full name
Heloisa Berti Gabriel
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Katzin, Alejandro Miguel (President)
Bargieri, Daniel Youssef
Cravo, Pedro Vitor Lemos
Miguel, Danilo Ciccone
Silveira Filho, José Franco da
Title in Portuguese
Caracterização funcional de farnesil difosfato sintase/geranilgeranil difosfato sintase (FPPS/GGPPS) e 1,4-dihidroxi-2-naftoato preniltransferase (MenA) envolvidas respectivamente na via de isoprenóides e da vitamina K em Plasmodium falciparum.
Keywords in Portuguese
Plasmodium
Enzimas
Isoprenóides
Malária
Menaquinona
Transfecção
Abstract in Portuguese
A malária é uma das principais e a mais disseminada das parasitoses humanas. A falta de uma vacina eficaz e o problema da resistência aos fármacos tem contribuído para o adiamento da solução do controle desta infecção. A busca de novos alvos biológicos tem se concentrado, em parte, na compreensão de vias metabólicas. Em P. falciparum, identificamos a biossíntese das duas formas da vitamina K (filoquinona e menaquinona). Na via MEP foram caracterizadas duas importantes enzimas bifuncionais, a farnesil difosfato sintase/geranilgeranil difosfato sintase (FPPS/GGPPS) capaz de formar farnesil difosfato e geranilgeranil difosfato e octaprenil pirofosfato sintase/fitoeno sintase (OPP/PSY) responsável pela biossíntese da cadeia isoprênica que se liga ao anel da via de ubiquinona, como também forma o primeiro caroteno na via de carotenóides. Este projeto tem como objetivo caracterizar o gene MenA da biossíntese de MQ, determinar a localização de FPPS/GGPPS em P. falciparum e investigar a importância de OPP/PSY e de FPPS/GGPPS no ciclo intraeritrocítico de P. falciparum.
Title in English
Functional characterization of farnesyl dyphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) and 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) respectively involved in the isoprenoid pathway and vitamin K in Plasmodium falciparum.
Keywords in English
Plasmodium
Enzymes
Isoprenoids
Malaria
Menaquinone
Transfection
Abstract in English
Malaria is one of the main widespread human parasites. The lack of an effective vaccine and the problem of drug resistance haves contributed to the delay of the control solution of this infection. The search for new biological targets has focused in part on the understanding of metabolic pathways. In P. falciparum, identified the biosynthesis of the two forms of vitamin K (phylloquinone and menaquinone). In the MEP pathway were characterized two important bifunctional enzyme, farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) able to form farnesyl diphosphate and geranylgeranyl diphosphate and octaprenyl pyrophosphate synthase/phytoene synthase (OPP/PSY) responsible for the biosynthesis of isoprenic side chains attached to the benzoquinone ring of ubiquinones, but also forms the first carotene in the carotenoid pathway. This project aims to characterize the MenA gene from the MQ biosynthesis, determine the localization of FPPS/GGPPS and investigate the importance of OPP/PSY and FPPS/GGPPS in intra-erythrocytic cycle of P. falciparum.
 
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Publishing Date
2016-02-24
 
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