tailieunhanh - Báo cáo khoa học: Molecular basis of the unusual catalytic preference for GDP/GTP in Entamoeba histolytica 3-phosphoglycerate kinase

Phosphoglycerate kinase (EC ) catalyzes reversible phosphoryl trans-fer from 1,3-bisphosphoglycerate to ADP to synthesize 3-phosphoglycerate and ATP during glycolysis. Phosphoglycerate kinases from several sources can use GDP⁄GTP as alternative substrates to ADP⁄ATP; however, the maximal velocities (Vm) reached with the guanine nucleotides are 50% of those displayed with the adenine nucleotides. | Molecular basis of the unusual catalytic preference for GDP GTP in Entamoeba histolytica 3-phosphoglycerate kinase Rusely Encalada1 Arturo Rojo-Dominguez2 Jose S. Rodriguez-Zavala1 Juan P. Pardo3 Hector Quezada1 Rafael Moreno-Sanchez1 and Emma Saavedra1 1 Departamento de Bioquimica Institute Nacionalde Cardiologia Mexico . Mexico 2 Departamento de Ciencias Naturales Unidad Cuajimalpa and Departamento de Quimica Unidad Iztapalapa Universidad Autonoma Metropolitana Mexico . Mexico 3 Departamento de Bioquimica Facultad de Medicina Universidad NacionalAutonoma de Mexico Mexico . Mexico Keywords ATP GTP synthesis glycolysis nucleotide selectivity parasite yeast Correspondence E. Saavedra Departamento de Bioquimica Instituto Nacionalde Cardiologia Juan Badiano No. 1 Col. Seccion XVI CP 14080 Tlalpan Mexico . Mexico Fax 52 55 5573 0994 Tel 52 55 5573 2911 ext 1298 E-mail emma_saavedra2002@ Received 14 November 2008 revised 23 January 2009 accepted 28 January 2009 doi Phosphoglycerate kinase EC catalyzes reversible phosphoryl transfer from 1 3-bisphosphoglycerate to ADP to synthesize 3-phosphoglycerate and ATP during glycolysis. Phosphoglycerate kinases from several sources can use GDP GTP as alternative substrates to ADP ATP however the maximal velocities Em reached with the guanine nucleotides are 50 of those displayed with the adenine nucleotides. By contrast Entamoeba histolytica phosphoglycerate kinase EC is the only reported phosphoglycerate kinase displaying higher activity with GDP GTP and lower affinities for the adenine nucleotides. To elucidate the molecular basis of the Entamoeba histolytica phosphoglycerate kinase selectivity for GDP GTP a conformational analysis was carried out on a homology model based on crystallographic structures of yeast and pig phosphoglycerate kinases. Some amino acid residues involved in the purine ring binding site not previously described were detected. .