Structural studies of human brain-type creatine kinase complexed with the ADP-Mg2+-NO3- -creatine transition-state analogue complex.
FEBS letters
confidence
Key findings
X-ray crystallography of hBB-CK with ligand-free, TSAC, and ADP-Mg2+ complexes reveals conformational changes triggered by ADP-Mg2+ binding; no clinical/biological endpoints.
View source on PubMed (PMID 18977227) ↗
- Population
- Structural study of human brain-type creatine kinase (hBB-CK) - in vitro crystallography
- Blinding
- not_reported
- Controls
- none
- Drug class
- supplement
Full abstract
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 (hBB-CK) were identified by X-ray crystallography: the ligand-free-form at 2.2A; the ADP-Mg2+, nitrate, and creatine complex (transition-state-analogue complex; TSAC); and the ADP-Mg2+-complex at 2.0A. The structures of ligand-bound hBB-CK revealed two different monomeric states in a single homodimer. One monomer is a closed form, either bound to TSAC or the ADP-Mg2+-complex, and the second monomer is an unliganded open form. These structural studies provide a detailed mechanism indicating that the binding of ADP-Mg2+ alone may trigger conformational changes in hBB-CK that were not observed with muscle-type-CK.