Induced fit in arginine kinase

Creatine kinase (CK) and arginine kinase (AK) are related enzymes that reversibly transfer a phosphoryl group between a guanidino compound and ADP. In the buffering of ATP energy levels, they are central to energy metabolism and have been paradigms of classical enzymology. Comparison of the open substrate-free structure of CK and the closed substrate-bound structure of AK reveals differences that are consistent with prior biophysical evidence of substrate-induced conformational changes. Large and small domains undergo a hinged 13°rotation. Several loops become ordered and adopt different positions in the presence of substrate, including one {residues 309-319) that moves 15 Å to fold over the substrates. The conformational changes appear to be necessary in aligning the two substrates for catalysis; in configuring the active site only when productive phosphoryl transfer is possible, and excluding water from the active site to avoid wasteful ATP hydrolysis.