INVESTIGADORES
FERNANDEZ Pablo Mariano
artículos
Título:
The Crystal Structure of Trypanosoma cruzi Arginine Kinase
Autor/es:
PABLO FERNANDEZ; A HAOUZ; C PEREIRA; C AGUILAR; P ALZARI
Revista:
PROTEINS: STRUCTURE, FUNCTION AND GENETICS
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2007 vol. 69 p. 209 - 209
ISSN:
0887-3585
Resumen:
Trypanosomes are protozoan organisms that cause im portant veterinary diseases and two of them are responsible for significant human diseases: Trypanosoma brucei is the agent of sleeping sickness (African trypanosomiasis) and T. cruzi causes Chagas disease in the American continent. Trypanosomes diverged early in evolution from other eukaryotes and posses unique features in terms of energetic metabolism. A peroxisome-like structure, the glycosome, contains most of the glycolytic and pentose phosphate pathway enzymes. In addition, the trypanosome mitochondria present unusual structure and functional properties that strongly depend on the different environments encountered by parasites.Arginine kinase (AK, E.C. 2.7.3.3) is a phosphotransferase that catalyzes the interconversion between phosphoarginine and ATP. This enzyme is present in some invertebrates, including the trypanosomatids, and represents an analogous system to the creatine kinases in vertebrates. Phosphagens such as phosphoarginine and phosphocreatine play a critical role as ‘‘energy storage’’ molecules because the high-energy phosphate can be rapidly transferred to ADP when the renewal of ATP is needed. Phosphagens support bursts of cellular activity until catabolic events such as glycogenolysis, glycolysis, and oxidative phosphorylation are switched on. In T. cruzi, AK overexpression was shown to increase the parasite survival capability under pH and nutritional stressconditions and seems to play a critical role as a regulator of energetic reserves and cell growth. A similar situation occurs when a heterologous AK is expressed in organisms lacking phosphagen kinases, such as yeast and bacteria. More recently, it was observed that T. cruzi epimastigotes treated with hydrogen peroxide showed a significant increase in both AK expression and survival capability during exposure, suggesting the participation of AK in the parasite response to oxidative stress.Although the crystal structures of several vertebrate creatine kinases are currently available, only a single AK has been structurally characterized so far, that of Limulus polyphemus (Horseshoe crab) AK. We have previously characterized the molecular and biochemical characterization of the T. cruzi AK (TcAK) and we report here the crystal structure of the ligand-free (open form) of the enzyme at 1.9 A ̊ resolution.
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