Volume 14 Issue 7, July 2018

Understanding how metals contribute to brain function is a major health priority. A new study combining pharmacology and genetics implicates the accumulation of copper in a brain arousal center as a regulator of zebrafish activity.

The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein degraders.

Single-molecule techniques combined with molecular dynamics simulations allowed visualization of a surprisingly high level of conformational homogeneity in the transport cycle of an ABC import system, BtuCD-F, and revealed an unexpected tight coupling of distinct conformational states responsible for vitamin B₁₂ binding, transport and release.

This Perspective explores the diversity, mechanisms and practical aspects of natural and engineered CRISPR-associated nucleases for genome engineering applications.

The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.

Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.

Computational protein design, without subsequent directed evolution, rapidly provides a set of aspartase variants capable of biocatalytic asymmetric addition of ammonia to substituted acrylates, producing various enantiopure β-amino acids.

Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein targets.

A genome-wide uracil profiling technology (termed “dU-seq”), based on selective labeling and biotin pull-down, reveals that uracil is enriched at the centromere of the human genome.

Structural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and DRG2.

A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.

Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.

A single-molecule approach combined with molecular dynamics simulations to examine the conformational dynamics of the Escherichia coli ABC transporter BtuCD defines a coordinated sequence of events leading to unidirectional transport.

Engineered erythropoietin receptor scaffolds equipped with extracellular sensor domains and modular intracellular domains that couple to endogenous signaling pathways enable modular reprogramming of designer membrane-bound receptors.

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.

Although the conversion of (7S)-salutaridinol 7-O-acetate to thebaine can occur spontaneously, the identification of a thebaine synthase enzyme that catalyzes the reaction indicates how nature avoids the formation of labile hydroxylated byproducts.