Volume 18 Issue 4, April 2022

Structural biology and resistance analyses reveal the binding mode and the basis for selective inhibition of the ATP synthase rotary motor protein by glycosylated macrolides.

Cell-free biosensing is emerging as an effective and low-cost technology, but interpretation and synthesis of the results remains largely manual. Now, researchers have incorporated a new information-processing layer between biosensors and their outputs using logic gates to integrate complex results.

Induced proximity is reshaping drug discovery. A new study debuts deubiquitinase-targeting chimeras (DUBTACs), small bifunctional molecules that co-opt a deubiquitinase to stabilize a target protein.

Photoaffinity analogs of a family of glycosylated macrolides, apoptolidins, revealed the F₁ subcomplex of mitochondrial ATP synthase as the target. Cryo-EM analysis of the apoptolidin–ATP synthase complex enabled identification of resistance mutations.

A survey of protein structures identifies widespread lysine–cysteine cross-links in functionally diverse proteins across all domains of life and in various structural motifs, where these redox switches control enzyme catalysis and/or ligand binding.

The high-resolution crystal structures of apo and self-alkylated ribozymes demonstrate the structural and biochemical basis of carbon–nitrogen bond formation between a specific guanine within the ribozyme and a 2,3-disubstituted epoxide substrate.

Equipping ROSALIND, a cell-free biosensing platform, with information processing circuits based on toehold-mediated DNA strand displacement enhances sensor performance and enables logic gate computation.

Computational and experimental analyses of the effects of spatial partitioning in microbial communities identify correlations between biodiversity and spatial context, offering experimental guidance for maintaining microbial community structures.

Iterative computational cycles of mutation and evaluation, modeling the process of directed evolution in silico, enable prediction of mutations that confer nucleic acid-binding activity onto an initial protein with no inherent function.

A targeted protein stabilization platform termed deubiquitinase-targeting chimera (DUBTAC) was developed based on heterobifunctional small molecules consisting of a deubiquitinase OTUB1 recruiter linked to a protein-targeting ligand.

K48-linked ubiquitin chains direct substrates for proteasomal degradation. Nakasone et al. provide the molecular basis for K48-linked ubiquitin chain synthesis by UBE2K and reveal a multivalent ubiquitin-binding mechanism of UBA in extending the ubiquitin chain.