Evolution of cooperativity in the phosphagen kinase family

Marisa P. McGinley, The College of Wooster

Abstract

The phosphagen kinase (PK) family of enzymes are widely distributed in various animal, protozoan, and bacterial taxa. They catalyze the reversible transfer of a phosphoryl group onto a guanidine acceptor and have an important role in cellular energy homeostasis. Two large groups dominate the PK family; arginine and creatine kinases. Arginine kinases (AK), which use arginine as the guanidine acceptor are found in bacterial and invertebrate organisms and typically function as monomeric enzymes. Conversely, creatine kinases (CK), which use creatine as their guanidine acceptor are found in some invertebrates and all vertebrates and are homodimeric enzymes. Recent studies have indicated that dimeric CKs may display cooperativity between subunits. This study adds to that work by investigating the nature of cooperativity in two species to better understand the possible evolution of this trait. Measurements of cooperativity using an isothermal titration calorimeter (ITC) were completed for the dimeric AK found in the sea cucumber, Stichopus japonicus and the dimeric CK in the sponge, Tethya aurantia. Scatchard plot analysis was used to interpret the ITC data and indicated that both of these enzymes display positive cooperativity. These findings indicate that cooperativity may have evolved in a common ancestor of both dimeric AK and CK. It also supports an evolutionary model in which common ancestor of AK and CK gave rise to dimeric AK as opposed to dimeric CK leading to dimeric AK.