Resistance to rifamycin antibiotics, which target bacterial RNA polymerases, is a growing problem. Here, the authors identify gene clusters from soil metagenomes encoding production of rifamycin analogues that are active against rifampicin-resistant bacteria through a d...

Significance Posttranslational protein modification by ubiquitin (Ub) regulates aspects of biology, including protein turnover and the cell cycle. Proteins and enzymes that promote Ub conjugation are therapeutic targets because they are sometimes dysregulated in cancer,...

The ATRX-DAXX histone chaperone complex incorporates H3.3 in heterochromatin in a replication-independent manner. Here, the authors present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX, and characterize ATRX-dependent and-ind...

The X-ray structure of the integral membrane protein isoprenylcysteine carboxyl methyltransferase suggests mechanisms by which it recognizes both water-soluble and membrane-bound reactants to catalyze the methylation of RAS and other CAAX proteins at the membrane-cytoso...

<jats:title>Abstract</jats:title><jats:p>The store-operated calcium (Ca<jats:sup>2+</jats:sup>) channel Orai governs Ca<jats:sup>2+</jats:sup> influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to depletion of Ca<j...

<jats:title>Abstract</jats:title> <jats:p>RNA-binding proteins (RBPs) play critical roles in cell homeostasis by controlling gene expression post-transcriptionally, contributing to mRNA processing events (splicing, polyadenylation, localization, stability, export and tr...

Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS cr...

Summary Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins such as small ubiquitin like modifier (SUMO) regulates processes including protein homeostasis, the DNA damage response, and the cell cycle. Proliferating cell nuclear an...

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08–2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochem...

The histone H3.3 chaperone DAXX is implicated in formation of heterochromatin and transcription silencing, especially for newly infecting DNA virus genomes entering the nucleus. Epstein-Barr virus (EBV) can efficiently establish stable latent infection as a chromatinize...