Determination of the crystallographic structure of Leishmania mexicana glucose-6-phosphate isomerase and comparision to the human enzyme

Author(s)

Artur Torres Cordeiro

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT)
• Defense date: 2004-04-16

Examining board members

Otavio Henrique Thiemann; Raghuvir Krishnaswamy Arni; Leila Maria Beltramini; Wim Maurits Sylvain Degrave; Igor Polikarpov

• Advisor: Otavio Henrique Thiemann

Abstract

This thesis presents a review about the occurrence of leishmaniasis in Brazil and all over the world. The main data sources were documents from Brazilian Health Ministry and the World Health Organization. The introduction presents actual information about strategies adopt by the parasite to evade the human immune response, the common drugs used in actual treatment, the need for new drugs based on a rational approach and the lack of interest from pharmaceutic industry to invest in research & development for tropical diseases. It also highlights the importance to identify, and validate possible metabolic targets before spending time and money in searching potential compounds that blocks a non validated parasite target. The enzymes that participate in the energy metabolism are considered good target. An example is the glicosomal enzyme phosphoglucose isomerase (PGI), which was recently validated by RNA interference experiments in T. brucei as a good target. The experiments described here intend to elucidate the crystallographic structure from L. mexicana PGI and compare its kinetic and structural proprieties to the human PGI. The mapping of the differences between both enzymes is crucial for the validation of PGI as a metabolic target and will assist in the design of inhibitors with high selectivity against the parasite enzyme. (AU)