E3 protein ligases enhance transfer of ubiquitin-like (Ubl) proteins from E2 conjugating enzymes to substrates by stabilizing the thioester-charged E2~Ubl in a closed configuration optimally aligned for nucleophilic attack. Here, we report biochemical and structural dat...

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...

Abstract Mycobacterium smegmatis FenA is a nucleic acid phosphodiesterase with flap endonuclease and 5′ exonuclease activities. The 1.8 Å crystal structure of FenA reported here highlights as its closest homologs bacterial FEN-family enzymes ExoIX, the Pol1 exonuclease ...

Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 a...

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottl...

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...

<jats:title>Abstract</jats:title> <jats:p>Mycobacterial Pol1 is a bifunctional enzyme composed of an N-terminal DNA flap endonuclease/5′ exonuclease domain (FEN/EXO) and a C-terminal DNA polymerase domain (POL). Here we document additional functions of Pol1: FEN activit...

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...

A 1.7 Å resolution co-crystal structure of U7BR from Schizosaccharomyces pombe in complex with Ubc7 is reported. Structural comparisons and biochemistry suggest that U7BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.