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Chemical proteomics analysis of human gastric cells revealed that infection with the stomach bacterium Helicobacter pylori decreases reactivity of legumain Cys219, which alters legumain processing and promotes xenograft tumor growth.
The use of NMR spectroscopy and development of a cellular BRET KRAS engagement assay revealed that noncovalent ligands can access the switch-II pocket of KRAS hotspot mutants.
Biochemical and structural characterization of a standalone ketosynthase, SalC, reveals that it serves as a critical intramolecular aldolase and β-lactone synthase during biosynthesis of the core of the marine natural product salinosporamide A.
The authors present the crystal structure of the MTR1 ribozyme that transfers the methyl group from O6-methylguanine to an adenine N1 in the target RNA and propose a catalytic mechanism based upon proximity, orientation and general acid catalysis.
The crystal structure of the methyltransferase ribozyme MTR1 reveals a cofactor-binding site reminiscent of purine riboswitches and suggests a catalytic mechanism involving nucleobase protonation, resulting in accelerated methyl transfer rates.
The cryo-EM structure of the Csy–dsDNA–AcrIF5 complex and biochemical analysis revealed that five AcrIF5 molecules bind to one Csy–dsDNA complex, destabilizing the helical bundle domain of Cas8f and preventing recruitment of Cas2/3.
Characterization of the polysaccharide utilization loci from two Bacteroides species from the human gut microbiota define biochemical and structural features underlying the catabolism of a hybrid algal polysaccharide found in edible seaweed.
Identification of venom insulins with A-chain elongations inspired hybrid analogs with similar activity to human insulin. Cryo-EM structure analysis revealed the basis of the hybrid peptide activity.
A patient-derived colorectal organoid drug screening platform was developed revealing an association between paclitaxel sensitivity and CHFR, a member of the spindle checkpoint component.
Fluorescence-quenched substrates, which accurately report on glycoside hydrolase activity, provide real-time activity measurements on α-GALA and α-NAGAL, including in fibroblasts from patients with linked lysosomal storage diseases.
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.
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.
Development of a multiplexed framework using metabolic changes from CRISPR interference in essential biological process genes combined with drug-induced metabolic changes enabled the identification of antibacterials with unique modes of action.
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.
Real-time fluorescence imaging analysis with a reconstitution system revealed binding dynamics of Hsp104/Ssa1/Sis1 chaperones to Sup35 amyloid and two distinct modes of amyloid disaggregation, fragmentation and dissolution.
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.
CQ31 inhibits the M24B aminopeptidases prolidase and Xaa-Pro aminopeptidase 1 leading to increased proline-containing peptides that block dipeptidyl peptidases 8 and 9 activity resulting in the activation of the CARD8 inflammasome.
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.
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.
Second-generation engineered soluble ACE2 proteins display enhanced binding to the spike protein of SARS-CoV-2 and operate as ‘decoys’ that interfere with viral infection, reduce lung injury and lower mortality in mouse models.