Beatrice D. Pilger

TL;DR: In this article, the mechanisms of substrate binding of HSV 1 TK were studied by means of site-directed mutagenesis combined with isothermal calorimetric measurements and guided by theoretical calculations and sequence comparison.

TL;DR: Analysis of the crystal structures and the molecular modeling presented in this paper suggest that T63 is essential for the binding of Mg2+ and thus the catalytic activity of the enzyme, while A168 limits steric accessibility and if mutated to a bulkier residue will exclude binding of larger substrate analogues.

TL;DR: TKHSV1(Y101F) shows a decrease in the quotient of the catalytic efficiency (kcat/KM) of dT over MCT corresponding to an increased specificity for MCT when compared to the wild-type enzyme.

TL;DR: In this paper, a site-directed mutagenesis study on Q125 was performed to clarify the contribution of this residue to the binding of thymidine or aciclovir beyond the hydrogen-bonding pattern observed in the crystal structure.

TL;DR: New derivatives of 9-(2-hydroxypropyl)-substituted adenine, chloropurine, hypoxanthine, guanine, thiopurines, and (methylsulfanyl)purine were synthesized and subjected to in vitro phosphorylation and binding affinity assays, revealing that hyp oxanthine derivatives represent a new class of TK substrates and thiopURine derivatives a newclass of Tk inhibitors.