Structural studies of human brain‐type creatine kinase complexed with the ADP–Mg 2+ –NO 3− –creatine transition‐state analogue complex

Creatine kinase is a member of the phosphagen kinase family, which catalyzes the reversible phosphoryl transfer reaction that occurs between ATP and creatine to produce ADP and phosphocreatine. Here, three structural aspects of human‐brain‐type‐creatine‐kinase ( h BB‐CK) were identified by X‐ray crystallography: the ligand‐free‐form at 2.2 Å; the ADP–Mg 2+ , nitrate, and creatine complex (transition‐state‐analogue complex; TSAC); and the ADP–Mg 2+ ‐complex at 2.0 Å. The structures of ligand‐bound h BB‐CK revealed two different monomeric states in a single homodimer. One monomer is a closed form, either bound to TSAC or the ADP–Mg 2+ ‐complex, and the second monomer is an unliganded open form. These structural studies provide a detailed mechanism indicating that the binding of ADP–Mg 2+ alone may trigger conformational changes in h BB‐CK that were not observed with muscle‐type‐CK.