Phosphagen (guanidino) kinases, including creatine kinase (CK), arginine kinase (AK), taurocyamine kinase (TK), lombricine kinase (LK), glycocyamine kinase (GK), and hypotaurocyamine kinase (HTK), are enzymes that catalyze the reversible transfer of the γ-phosphoryl group of adenosine triphosphate (ATP) to naturally occuring guanidino compounds such as creatine, arginine, yelding adenosine diphosphate (ADP) and a phosphorylated guanidine typically referred to as phosphagen (phosphocreatine, phosphoarginine and etc). Members of this enzyme family play a key role in animals as ATP-buffering systems in cells that display high and variable rates of ATP turnover. Phosphagen kinases have been found in all animal species and in some protozoa, such as trypanosomes, choanoflagellates, and the ciliates, Paramecium tetraurelia, Paramecium caudatum, and Tetrahymena. Eukaryotic phosphagen kinases consist of a small, ~100-residue, α-helical N-terminal domain and a larger, 250+-residue, C-terminal α/β saddle domain in which many key residues involved in catalysis are found (see <PDB:3L2E>). The N-terminal domain undergoes significant conformational movements during catalysis, closing down on the catalytic pocket. It is involved in dimer formation. Bacterial phosphagen kinases have the large C-terminal domain seen in eukaryotic phosphagen kinases but lack the N-terminal domain [1,2,3,4].

A cysteine residue is implicated in the catalytic activity of these enzymes. The region around this active site residue is highly conserved and can be used as a signature pattern. We also developed two profiles, which cover respectively the entire phosphagen kinase N- and C-terminal domains.