Mechanism of Nucleotide-Dependent Allosteric Regulation in Aspartate Transcarbamoylase.

Discovered nearly 70 years ago, the allosteric regulation of aspartate transcarbamoylase (ATCase) is discussed in every biochemistry textbook. ATCase catalyzes the first step in pyrimidine biosynthesis. Despite extensive research, the mechanism by which this enzyme is regulated by pyrimidine and purine nucleotides has remained elusive.

Introduction to diffuse scattering and data collection.

A long-standing goal in X-ray crystallography has been to extract information about the collective motions of proteins from diffuse scattering: the weak, textured signal that is found in the background of diffraction images. In the past few years, the field of macromolecular diffuse scattering has seen dramatic progress, and many of the past challenges in measurement and interpretation are now considered tractable. However, the concept of diffuse scattering is still new to many researchers, and a general set of procedures needed to collect a high-quality dataset has never been described in detail.

Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II.

Etoposide is a broadly employed chemotherapeutic and eukaryotic topoisomerase II poison that stabilizes cleaved DNA intermediates to promote DNA breakage and cytotoxicity. How etoposide perturbs topoisomerase dynamics is not known. Here we investigated the action of etoposide on yeast topoisomerase II, human topoisomerase IIα and human topoisomerase IIβ using several sensitive single-molecule detection methods.