Kinase phosphate-binding residues

Although most of the conserved phosphate-binding residues in the ATP-binding site are crucial for the catalytic process, they do not contribute much to the free energy of binding of the ATP kinase, which is nicely reflected in the equipotent affinity of PKA for ATP, ADP, and adenosine [10],... 

Zhou, L. Thornburg, R. Site-specific mutations of conserved residues in the phosphate-binding loop of the Arabidopsis UMP/CMP kinase alter ATP and UMP binding. Arch. Biochem. Biophys., 358, 297-302 (1998)... 

The reaction of X with S must be fast and reversible, close to if not at equilibrium with concentration of S. It can be that there is an intermediate step in which X binds to a protein kinase (a protein which phosphorylates other proteins mostly at histidine residues in bacteria) using phosphate transferred from ATP. It then gives XP which is the transcription factor, where concentration of S still decides the extent of phosphorylation. No change occurs in DNA itself. Here equilibrium is avoided as dephosphorylation involves a phosphatase, though changes must be relatively quick since, for example, cell cycling and division depend on these steps, which must be completed in minutes. We have noted that such mechanical trigger-proteins as transcription factors are usually based on a-helical backbones common to all manner of such adaptive conformational responses (Section 4.11). 

Figure 11.2 Structure of the insulin receptor (a). Binding of insulin promotes autophosphorylation of the (3-subunits, where each (3-subunit phosphorylates the other (3-subunit. Phosphate groups are attached to three specific tyrosine residues (tyrosines 1158, 1162 and 1163), as indicated in (b). Activation of the (3-subunit s tyrosine kinase activity in turn results in the phosphorylation of various intracellular (protein) substrates which trigger the mitogen-activated protein kinase and/or the phosphoinositide (PI-3) kinase pathway responsible for inducing insulin s mitogenic and metabolic effects. The underlying molecular events occurring in these pathways are complex (e.g. refer to Combettes-Souverain, M. and Issad, T. 1998. Molecular basis of insulin action. Diabetes and Metabolism, 24, 477-489)...

Protein kinases have a general architecture catalytic domain, a binding domain that orients the substrate to the catalytic site, and phosphate donor binding site which donates the y-phosphate to the acceptor hydroxyl residues. 

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