Structural and dynamics analysis of pyruvate kinase from erythrocytes: implications in pathology

Abstract

Our current study revolves around the dynamic characterization of the human erythrocyte pyruvate kinase (RPYK). The deficiency of this protein is a common cause of nonspherocytic hemolytic anemia, a rare, autosomal recessive disease. We plan to perform a comprehensive set of molecular dynamics simulations of both the wildtype (WT) and mutant variants of R-PYK in different conditions, in order to explore the dynamic behavior of the enzyme, describe the function and allosteric mechanism in terms of its dynamics fingerprint and identify altered dynamic behavior of the known pathogenic variants of the enzyme.