tailieunhanh - Báo cáo khoa học: The crystal structure of glucose-6-phosphate isomerase from Leishmania mexicana reveals novel active site features

Glucose-6-phosphate isomerase catalyzes the reversible aldose-ketose isomerization of D-glucose-6-phosphate to D-fructose-6-phosphate in glycolysis and gluconeogenesis, and in the recycling of hexose-6-phosphate in the pentose phosphate pathway. The unicellular protozoans,Trypan-osoma brucei, T. cruziandLeishmaniaspp., of the order Kinetoplastida are important human parasites responsible for African sleeping sickness, Chagas’ disease and leish-maniases, respectively. In these parasites, glycolysis is an important (and in some cases the only) metabolic pathway for ATP supply | Eur. J. Biochem. 271 2765-2772 2004 FEBS 2004 doi The crystal structure of glucose-6-phosphate isomerase from Leishmania mexicana reveals novel active site features Artur T. Cordeiro1 Paul A. M. Michels2 Luiz F. Delboni3 and Otávio H. Thiemann1 1Laboratory of Protein Crystallography and Structural Biology Physics Institute of Sao Carlos University of Sao Paulo Sao Carlos-SP Brazil 2Research Unit for Tropical Diseases and Laboratory of Biochemistry Christian de Duve Institute of Cellular Pathology Brussels Belgium 3Pontificia Universidade Catolica de Minas Gerais Popos de Caldas-MG Brazil Glucose-6-phosphate isomerase catalyzes the reversible aldose-ketose isomerization of D-glucose-6-phosphate to D-fructose-6-phosphate in glycolysis and gluconeogenesis and in the recycling of hexose-6-phosphate in the pentose phosphate pathway. The unicellular protozoans Trypanosoma brucei T. cruzi and Leishmania spp. of the order Kinetoplastida are important human parasites responsible for African sleeping sickness Chagas disease and leishmaniases respectively. In these parasites glycolysis is an important and in some cases the only metabolic pathway for ATP supply. The first seven of the 10 enzymes that participate in glycolysis as well as an important fraction of the enzymes of the pentose phosphate pathway are compartmentalized in peroxisome-like organelles called glycosomes. The dependence of the parasites on glycolysis the importance of the pentose phosphate pathway in defense against oxidative stress and the unique compartmentalization of these pathways point to the enzymes contained in the glycosome as potential targets for drug design. The present report describes the first crystallographic structure of a parasite Leishmania mexicana glucose-6-phosphate isomerase. A comparison of the atomic structure of L. mexicana human and other mammalian PGIs which highlights unique features of the parasite s enzyme is presented. Keywords Leishmania .

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