Apicomplexan parasites depend heavily on glycolysis for energy. This is particularly true of in the case of Cryptosporidium parvum which is missing a functional mitochondrion. Pyruvate kinase (PyrK) catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, is a central metabolic regulator in most organisms. In mammals, there are four PyrK isozymes. In Plasmodium and Toxoplasma, there is one cytoplasmic PyrK and another one localized in the apicoplast. In contrast, only the cytoplasmic isozyme is known to exist in C. parvum.
Crystal structures of PyrK from humans (PDB ID: 3QGY) as well as T. gondii (PDB ID: 3EOE, 3GG8 [1]), Leishmania mexicana (PDB ID: 3E0V), Trypanosoma cruzi (PDB ID: 3QV9), T. brucei (PDB ID: 2X0S) and P. falciparum (PDB ID: 3KHD) have been previously reported. We show here the structure of C. parvum pyruvate kinase. As reported by Cook et al [3], another group also solved the structure of this same enzyme (PDB ID: 4DRS). Interestingly, their structure features an intermolecular disulfide bond not seen in ours.
