Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.

Uracil DNA-glycosylase (UNG) is a DNA repair enzyme that removes the highly mutagenic uracil lesion from DNA using a base flipping mechanism. Although this enzyme has evolved to remove uracil from diverse sequence contexts, UNG excision efficiency depends on DNA sequence. To provide the molecular basis for rationalizing UNG substrate preferences, we used time-resolved fluorescence spectroscopy, NMR imino proton exchange measurements, and molecular dynamics simulations to measure UNG specificity constants (k/K) and DNA flexibilities for DNA substrates containing central AUT, TUA, AUA, and TUT motifs.

A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.

TRPV1 is a polymodal receptor ion channel that is best known to function as a molecular thermometer. It is activated in diverse ways, including by heat, protons (low pH), and vanilloid compounds, such as capsaicin. In this review, we summarize molecular studies of TRPV1 thermosensing, focusing on the cross-talk between heat and other activation modes.