Possible Interaction: Adenosine Triphosphate and Histidine

“A corresponding histidine insertion into the Gld2 active site alters substrate specificity from ATP to UTP.”

“ Histidine raised the ATP level to 73% and the creatine phosphate level to 68% of normal control during reperfusion.”

“This suggests a regulatory role for ATP that may be important for modulating competition for shared resources between the metabolic processes of L-histidine and coformycin biosynthesis.”

“In the slower nucleoside binding step, a conserved histidine in the HxxH motif orients the incoming ATP through base-stacking interactions resulting in a deep minimum in the free energy surface.”

“We, therefore propose that the difference in the catalytic efficiency of these two constructs is due to the interference of ATP binding by the histidine tag at the amino—terminus of nsp13.”

“The study of the variation in the energy during the mutual approach of the His and ATP to form adenylate shows that the surrounding nanospace of synthetase confines the reactants (L-His and ATP) and proximally places in a geometry suitable for the in-line nucleophilic attack.”

“The charge distributions on the His and ATP are important for the discrimination.”

“In the former, stacking interaction between the aromatic moiety of ATP and the imidazole ring of l-histidine is crucial to the adduct stability.”

“When both types … this complex with ATP … histidine destabilizes the complex, resulting in a shift to multiple species in equilibrium with an average of 9.3 S. While this … elicited by substrates and inhibitors suggests the presence of allosteric regulatory mechanisms reminiscent of other multisubunit enzymes of metabolic importance.”

“ Histidine regulates the operation of this cycle by inhibiting the enzyme that catalyzes the condensation of ATP and PP-ribose-P; hence, purine nucleotides are shunted into the cycle only to the extent that they are needed for histidine biosynthesis (2, 3).”