Volume 13 Issue 10, October 2017

Kinetochores form the critical interface with spindle microtubules that accounts for chromosome movement and segregation fidelity during mitosis. Spatial and temporal control of motor protein and checkpoint signaling at kinetochores is now possible with a new set of optogenetic tools.

The introduction of a cyclopropyl group is critical for imparting colibactin with the ability to cleave DNA. Nonribosomal peptide synthetase ClbH and polyketide synthase ClbI are now shown to work in concert to convert S-adenosylmethionine into this cyclopropyl group.

Genome mining reveals a new ribosomally synthesized and post-translationally modified peptide (RiPP) from Klebsiella pneumoniae. This new antibiotic inhibits bacterial ribosomes by obstructing the peptide exit tunnel, and its modular nature presents a unique opportunity for future engineering of antibacterial drugs.

A nonribosomal peptide synthetase involved in colibactin biosynthesis utilizes S-adenosylmethionine as a nonproteinogenic amino acid building block, which is then converted into the cyclopropane moiety that is critical for colibactin's genotoxic activity.

Biochemical characterization and mutagenesis of Trt14 with a series of substrate and intermediate analogs, plus structural analysis of Trt14 and two homologs, reveal how the enzyme catalyzes D-ring rearrangement during meroterpenoid biosynthesis.

The pyrophosphate analog imidodiphosphate (PNP) alters the reaction equilibrium of human DNA polymerase β, and the resulting increase in the rate of pyrophosphorolysis enables kinetic and structural dissection of this reverse reaction of the enzyme.

Bisphosphoglycerate mutase (BPGM) drives phosphoglycerate mutase 1 (PGAM1) phosphorylation, which is required for glycolytic flux. Loss of BPGM is partially compensated by 1,3-BPG directly phosphorylating PGAM1, sustaining glycolytic flux but diverting metabolites for serine synthesis.

Structure-guided engineering of an NADH oxidase switches its cofactor preference, thus yielding an NADPH oxidase that can be used to tune the cellular NADP⁺/NADPH ratio and to examine the links between mitochondrial NADH and NADPH pools.

The development of two new optogenetic dimerizers—CTH, which promoted uncaging with less light and longer wavelengths, and TNH, a reversible dimerizer—enabled spatial and temporal manipulation of kinetochore-mediated checkpoint signaling and transport of chromosomes to the spindle equator.

Inhibitors of CDK8 enhance IL-10 production during innate immune activation in human and mouse primary macrophages and dendritic cells via diminished phosphorylation of the c-Jun subunit of the AP-1 transcription regulatory complex.

A combination of bulk and single-molecule FRET, as well as cleavage activity assays, reveals that the twister ribozyme requires more Mg²⁺ for folding than it does for self-cleavage, and is also more efficiently activated by several transition metals.

Crystal structures of the HIV-1 Env trimer with cell-entry inhibitor antiviral drug leads BMS-378806 and BMS-626529 along with biophysical data define allosteric and competitive mechanisms to inhibit CD4-induced structural changes in Env.

Lytic polysaccharide monooxygenases (LPMOs) catalyze the oxidative cleavage of polysaccharides. Identification of a hydrogen peroxide–dependent pathway for sugar oxidation by these enzymes challenges the prevailing model that LPMOs are oxygen-dependent monooxygenases.

Identification of the antibiotic peptide KLB, from Klebsiella pneumoniae, which inhibits the growth of various Gram-negative bacteria by binding the nascent peptide exit tunnel on the large ribosomal subunit in a compact curled conformation, thereby stalling translation.