Structural studies of human brain-type creatine kinase complexed with the ADP-Mg2+-NO3- -creatine transition-state analogue complex.
Level 5 - mechanism / opinion, no new human data
In vitro structural biology study (X-ray crystallography)
PubMed 18977227 · doi:10.1016/j.febslet.2008.10.039
What was done
X-ray crystallography was used to determine the structures of human brain-type creatine kinase (hBB-CK) across three states: unliganded, bound to a transition-state analogue complex (ADP-Mg2+, nitrate, and creatine; TSAC), and bound to ADP-Mg2+ alone.
What was found
The ligand-free structure was resolved at 2.2 Å and the ADP-Mg2+ complex at 2.0 Å (resolution for TSAC was not reported in the abstract). Ligand-bound hBB-CK homodimers exhibited an asymmetrical state consisting of one closed monomer (bound to TSAC or ADP-Mg2+) and one unliganded open monomer. Binding of ADP-Mg2+ alone triggered conformational changes in hBB-CK that are absent in muscle-type creatine kinase.
Why it matters
These findings identify isoform-specific conformational dynamics of human brain creatine kinase, clarifying how cofactor binding primes the catalytic mechanism.
Limits
The study is restricted to in vitro static crystal structures and does not provide real-time kinetic measurements, physiological turnover rates, or in vivo functional data.
Cited by
- supports Enzymes that transfer phosphate groups from phosphocreatine to ADP to produce ATP require magnesium as a cofactor.