Creatine metal complexes

Such studies on creatine kinase (Eq. 12-31) utilized both a bound Mn2+ ion and a nitroxide spin label to estimate distances of various protons from the nitroxide.683 Together with EPR measurements (Box 8-C), which gave the Mn2+-nitroxide distance, a model of the ATP Mn2 complex in the active site was constructed. Additional EPR experiments on Mn2+ complexes with ATP and ADP containing 170 in the a, (3, or y phospho groups showed that in the enzyme ATP creatine complex the metal ion is bound to all three phospho groups of ATP. It remained coordinated with the two phospho groups of ADP and also that of the phospho-creatine product in the enzyme ADP creatine-P complex as well as in the transition state, which is pictured occurring via a metaphosphate ion.684... 

Metal cofactors do not always bind to the enzyme but rather bind to the primary substrate. The resulting substrate-metal complex binds to the enzyme and facilitates its activity. Creatine kinase catalyses the transfer of phosphoryl groups from adenosine triphosphate (ATP), which is broken down to adenosine diphosphate (ADP). The reaction requires the presence of magnesium ions. These, however, do not bind to the enzyme but bind to ATP, forming an ATP Mg complex. It is this complex that binds to the enzyme and allows transfer of the phosphoryl group ... 

The second mode of toxicity is postulated to involve the direct interaction of the epidithiodiketopiperazine motif with target proteins, forming mixed disulfides with cysteine residues in various proteins. Gliotoxin, for example, has been demonstrated to form a 1 1 covalent complex with alcohol dehydrogenase [13b, 17]. Epidithiodi-ketopiperazines can also catalyze the formation of disulfide bonds between proxi-mally located cysteine residues in proteins such as in creatine kinase [18]. Recently, epidithiodiketopiperazines have also been implicated in a zinc ejection mechanism, whereby the epidisulfide can shuffle disulfide bonds in the CHI domain of proteins, coordinate to the zinc atoms that are essential to the tertiary structure of that domain, and remove the metal cation [12d, 19],... 

ORD and CD spectra of creatine phosphokinase and of its complexes with adenine nucleotides, both in the absence and presence of metal ions... 

It is generally accepted that the bivalent activating metal ion does not have a bridging role in reactions of creatine kinase thus, the M +-nucleotide complex is a substrate but there is minimal interaction between and the enzyme. Gabriel and... 

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