Despite its high similarity with monomeric arginine kinase, muscle creatine kinase is only enzymatically active as a dimer

Dynamical properties of the loop 320s of substrate‐free and substrate‐bound muscle creatine kinase by NMR

“…This hypothesis of cooperative binding is in line with some reports of the chemical modification of C282 -the active site cysteine -which suggest a functional asymmetry of MCK monomers [16,17]. Because conflicting results have been obtained about the role of quaternary organization for the expression of catalytic activity [18][19][20], a structural and functional asymmetry would be a good rationale to explain why CK isoenzymes have to be at least dimers for full enzymatic activity. However, most cysteine-specific reagents fully inactivate MCK with a single kinetic phase and both active sites are protected against cysteine modification in the TSAC form [7].…”

“…Whereas AKs are monomers, CK isoenzymes, as well as several other GKs, have dimeric, or octameric, quaternary structures. However, this propensity towards higher molecular mass does not provide CK isoenzyme with any obvious advantage over their monomeric AK counterparts [18] and there are no clear clues as why CK isoenzymes form dimeric structures. Mainly based on crystallization data, it has been proposed that dimeric GKs could follow a reciprocating mechanism according to which only one of the subunits is allowed to reach the transition-state conformation at a time [1].…”

Macro Ck2 Accumulation in Tenofovir-Treated HIV Patients is Facilitated by Ck Oligomer Stabilization but is Not Predictive for Pathology

“…The octameric form is largely predominant in vivo, but readily dissociates into dimers in a concentration-, pH-and temperature-dependant manner [4,11] or as a result of oxidative stress [54,55]. No other uMtCK oligomers occur in vivo, and inactive monomers only form under denaturating conditions [26,56]. The molecular structure of human uMtCK reveals that octamers are stabilized by hydrophobic interfaces and additional polar interactions between the N-termini of neighbouring dimers [25].…”

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni

“…However, a dimeric GK with an asymmetric structure in the substrate-free form and a doubly closed structure in the GK-TSA complex have also recently been described (27), ruling out the hypothesis of a systematic coupling between asymmetrical unliganded dimers and catalytically interdependent monomers. In addition, several experiments performed on muscle CK did not provide any evidence for a functional asymmetry of the two identical subunits of the enzyme (30,31,36,37).…”