The role of the C8 proton of ATP in the regulation of phosphoryl transfer within kinases and synthetases.

ABSTRACT:

Background

The kinome comprises functionally diverse enzymes, with the current classification indicating very little about the extent of conserved regulatory mechanisms associated with phosphoryl transfer. The apparent Km of the kinases ranges from less than 0.4 μM to in excess of 1000 μM for ATP. It is not known how this diverse range of enzymes mechanistically achieves the regulation of catalysis via an affinity range for ATP varying by three-orders of magnitude.

Results

We have demonstrated a previously undiscovered mechanism in kinase and synthetase enzymes where the overall rate of reaction is regulated via the C8-H of ATP. Using ATP deuterated at the C8 position (C8D-ATP) as a molecular probe it was shown that the C8-H plays a direct role in the regulation of the overa

SUBMITTER: Kenyon CP 

PROVIDER: S-EPMC3145573 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature