Volume 13 Issue 8, August 2017

Peroxidases, rather than simply reducing H₂O₂ to water, also convey oxidation signals to proteins such as transcription factors. A new study reveals how a scaffold protein enables formation of a mixed disulfide between the peroxidase and a transcription factor.

New structures of the glucagon-like peptide-1 (GLP-1) and glucagon receptors in complex with peptide and nonpeptide ligands provide a comprehensive, detailed picture of the molecular mechanisms of action of family B GPCRs. This opens the door for true structure-based drug discovery aimed at both novel orthosteric and allosteric subsites of the receptors.

The genome of the poisonous mushroom Omphalotus olearius provides a potent new biocatalytic strategy for installing backbone N-methyl amides on ribosomally synthesized peptides. This discovery could yield new biotechnologies for drug development from peptide macrocycles.

The organelles and subcellular compartments of yeast provide distinct environments and physical separation from the cytosol, enabling opportunities to target biosynthetic pathways to these compartments and enhance production of desirable compounds.

Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-N-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.

Characterization of the heme-dependent enzyme KtzT reveals it to be the elusive enzyme responsible for nitrogen–nitrogen bond formation during the biosynthesis of piperazate, a building block for some nonribosomal peptide natural products.

Cpf1 is a CRISPR effector protein that exhibits greater genome editing specificity than Cas9 nuclease. Cpf1 from two distinct bacteria selectively processes RNA polymerase II transcripts into crRNA fragments competent for genome editing.

A genetically encoded unnatural amino acid analog and its acidic deprotection enable the site-specific incorporation of phosphotyrosine (pTyr) into proteins such as ubiquitin, where it can be used to study the function of this phosphorylated residue.

A propeptide strategy increases uptake of phosphotyrosine and a nonhydrolyzable analog to facilitate their incorporation into proteins by recombinant methods, aided by a specific aminoacyl-tRNA synthetase with a reconfigured active site.

High-throughput screening and structure-guided design identified small-molecule inhibitors that prevent the interaction between N-terminally acetylated E2 conjugating enzyme UBE2M and DCN1, an E3 ligase for the ubiquitin-like protein Nedd8.

MetA and MetX are phylogenetically unrelated families of acyl-L-homoserine transferases. Experimental assignation of function and structural modeling of these families correct widespread misannotation, reveal convergence of function and uncover new functions in a subclass of MetX.

Synthesis and application of activity-based probes based on cyclophellitol enabled the cellular profiling of β-glucuronidase activity and revealed an unexpected feature of endo-acting heparanase processing.

Biochemical and structural analysis, combined with metadynamics simulations, illustrate how a single amino acid substitution switches a β-glycosidase from a double S_N2 mechanism to a front-face S_Ni-like mechanism.

An inactive mutant of a bacterial O-GlcNAc hydrolase was used as an affinity reagent to enrich O-GlcNAc-modified proteins from Drosophila embryos and led to the identification, by MS–proteomics, of O-GlcNAcylated proteins involved in embryogenesis.

Phosphorothioate (PT) DNA modifications in E. coli and Salmonella are turned over to maintain bacterial fitness through decreased susceptibility to genomic instability caused by hypochlorous-acid-mediated PT oxidation.

Coupling the use of artificial chromosomes with metabolomics enables the high-throughput linkage of fungal natural products with their biosynthetic gene clusters. This method was used here to identify a novel polyketide–nonribosomal peptide scaffold.

AFM is used to show that curli, the functional amyloid fibrils generated by bacteria, form by polar growth from a one-step nucleation of monomers into minimal fibril units without transitioning through an intermediate, non-amyloid oligomeric state.

The H₂O₂-responsive transcription factor Yap1 undergoes oxidative activation mediated by the peroxidase Orp1. In vitro reconstitution of the redox relay revealed a role for the Yap1-binding protein Ybp1 in promoting the formation of a ternary complex with Orp1 and Yap1 to enable redox transfer.

Cylindrocyclophane biosynthesis involves an unexpected halogenated intermediate arising from chlorination of an unactivated carbon center by a halogenase, followed by dimerization through stereospecific enzymatic alkylation of resorcinol aromatic rings.