Volume 11 Issue 5, May 2015

Single-step site-specific labeling of native proteins is one of the holy grails in the chemical biology field. 2-Pyridinecarboxyaldehyde derivatives are shown to react selectively at the N terminus of proteins to form stable conjugates, irrespective of the nature of the N-terminal amino acid, enabling the straightforward introduction of useful functional groups into a wide array of proteins.

Cytosolic proteins can be modified cotranslationally by the installation of O-GlcNAc groups onto serine and threonine residues. This modification suppresses cotranslational ubiquitination and stabilizes proteins against proteasomal degradation.

Spider silks have enormous potential as strong yet flexible biomaterials, but obtaining artificial silk polymers has proven challenging. Recent advances in our understanding of natural silk processing may inform techniques for silk production.

Post-translational regulation of Cas9 activity may improve the specificity of genomic targeting. A modified version of Cas9 with an insertion of a small molecule–regulated intein allows temporal control of Cas9 activity and reduces off-target activity.

O-GlcNAcylation is a known post-translational modification, but analysis of nascent proteins now demonstrates that it also occurs during translation, preventing proteolytic degradation of modified proteins by blocking ubiquitination.

Bioconjugation methods enable a variety of applications, but it remains difficult to modify many proteins in a single location with a single functional group. A serendipitous discovery of aldehyde reactivity now leads to reagents for the selective labeling of protein N termini under mild conditions.

The lack of existing tools has made it difficult to detect and quantify methionine sulfoxide in cells. The introduction of the MetSOx and MetROx fluorescent sensors allows detection of stereospecific forms of methionine sulfoxide in cells.

The orphan nuclear receptor Nur77 blocks inflammation through inhibition of p65 DNA binding and is suppressed by p38α-mediated phosphorylation. A small-molecule compound, PDNPA, disrupts p38α-Nur77 interactions and alleviates mouse models of sepsis.

An siRNA screen for genes that suppress mutant huntingtin toxicity in both mammalian cells and Drosophila identifies glutaminyl cyclase (QPCT). Newly generated small-molecule inhibitors further identify QPCT as a druggable target for Huntington′s disease.

Genetic, biochemical and bioinformatic data define a pathway in Archaea that links the ribose moieties of nucleosides to central carbon metabolism, substituting for the classical pentose phosphate pathway found in Bacteria and Eukarya.