the crystal structure of toxoplasma gondii pyruvate kinase 1刚地弓形虫丙酮酸激酶1的晶体结构.pdfVIP

The Crystal Structure of Toxoplasma gondii Pyruvate Kinase 1 1,2 1 1 1 1 Rebecca Bakszt , Amy Wernimont , Abdellah Allali-Hassani , Man Wai Mok , Tanya Hills , Raymond 1 1 Hui , Juan C. Pizarro * 1The Structural Genomics Consortium (SGC), University of Toronto, Toronto, Ontario, Canada, 2 Molecular Biotechnology, Department of Physics and Measurement ¨ ¨ Technology, Biology and Chemistry (IFM), Linkoping University, Linkoping, Sweden Abstract Background: Pyruvate kinase (PK), which catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, is a central metabolic regulator in most organisms. Consequently PK represents an attractive therapeutic target in cancer and human pathogens, like Apicomplexans. The phylum Aplicomplexa, a group of exclusively parasitic organisms, includes the genera Plasmodium, Cryptosporidium and Toxoplasma, the etiological agents of malaria, cryptosporidiosis and toxoplasmosis respectively. Toxoplasma gondii infection causes a mild illness and is a very common infection affecting nearly one third of the world’s population. Methodology/Principal Findings: We have determined the crystal structure of the PK1 enzyme from T. gondii, with the B domain in the open and closed conformations. We have also characterized its enzymatic activity and confirmed glucose-6- phosphate as its allosteric activator. This is the first description of a PK enzyme in a closed inactive conformation without any bound substrate. Comparison of the two tetrameric TgPK1 structures indicates a reorientation of the monomers