C.H. Arrowsmith

Chemically induced USP21-KLHL12 association recruits USP21 to COPII assembly

The paper shows that BAY-805 induces USP21-KLHL12 association, recruiting USP21 to COPII vesicles and impairing large cargo transport.

Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human Type II Transmembrane Serine Proteases

This study shows HAI-2 inactivates TTSPs only after zymogen activation, revealing a novel mechanism for regulating these proteases and suggesting therapeutic applications.

An Atlas of Short Linear Motif-Mediated Human Protein-Protein Interactions

The paper maps over 20,000 human protein-protein interactions mediated by short linear motifs using a peptide library screening approach.

High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds

The paper uses high-throughput affinity-selection mass spectrometry to identify protein targets of ToxCast and PFAS compounds, discovering novel interactions and revealing distinct binding patterns of legacy and replacement PFAS.

Large-scale discovery, analysis, and design of protein energy landscapes

The paper measures conformational fluctuations of protein domains using hydrogen-deuterium exchange mass spectrometry and uses computational modeling to design mutations that stabilize low-stability segments.

Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22

This paper reveals the structural basis of NSD2 degradation via SCF-FBXO22 recruitment, showing how aldehyde-based degraders induce conformational changes for covalent binding and efficient protein degradation.

Direct-to-Biology Enables Rapid Identification of Potent FBXO22 Degraders

The paper tests PROTACs targeting FBXO22 and finds no degradation of four targets but identifies potent FBXO22 homo-PROTACs and CRBN/VHL-mediated degraders.

Development of a dual chemical probe for the USP16 and HDAC6 zinc-finger ubiquitin-binding domain

The paper develops a chemical probe targeting the USP16 zinc-finger ubiquitin-binding domain and evaluates its selectivity and activity in cellular assays.

Glioblastoma stem cells show transcriptionally correlated spatial organization

The paper shows that glioblastoma stem cells form spatial patterns correlated with their transcriptional state, using image analysis to link morphology and gene expression.

Enantioselective Protein Affinity Selection Mass Spectrometry (E-ASMS)

This study introduces E-ASMS, a method to detect weak binders and assess enantioselectivity, identifying 16 binders across 12 human protein targets with confirmed binding mechanisms.

Identification and Characterization of a Small Molecule Ligand for the Huntingtin-HAP40 Complex

The paper identifies a small molecule ligand for the HTT-HAP40 complex using AS-MS and validates its binding through multiple techniques, highlighting a druggable interface for HD therapeutics.

Cathepsin K as a Key Protease in Processing of SARS-CoV-2 Spike Activation Sites and a Target of Dual-Inhibition

This study identifies Cathepsin K as a key host protease for SARS-CoV-2 spike activation and shows it can be inhibited by existing drugs.

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

This paper introduces ProtacID, a BioID-based method to identify PROTAC-proximal proteins, validates degradation targets, and identifies non-productive interactions in human cells.

An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity

The paper describes the enantioselective resolution of a chemical probe targeting CHIKV nsP2 helicase, showing potent antiviral activity for one enantiomer and low activity for the other.

Structural basis of TMPRSS11D specificity and autocleavage activation

The paper determines the structural basis of TMPRSS11D autocleavage activation and shows that nafamostat mesylate is cleaved by TMPRSS11D, reducing its efficacy as a protease inhibitor.

Identification of Direct-acting nsP2 Helicase Inhibitors with Anti-alphaviral Activity

This paper identifies and optimizes oxaspiropiperidine inhibitors targeting nsP2hel, showing nanomolar antiviral activity against multiple alphaviruses.

Potent and Selective SETDB1 Covalent Negative Allosteric Modulator Reduces Methyltransferase Activity in Cells

The paper identifies UNC10013, a covalent ligand targeting SETDB1's 3TD domain, which reduces methyltransferase activity and shows selectivity in cells.

CACHE Challenge #1: targeting the WDR domain of LRRK2, a Parkinson's Disease associated protein.

The paper evaluates computational hit-finding methods for targeting the WDR domain of LRRK2, a Parkinson's disease protein, finding that diverse strategies yielded weakly potent compounds.

A resource to enable chemical biology and drug discovery of WDR Proteins

The paper develops a resource for discovering ligands for WDR proteins using experimental and computational methods, leading to the identification of drug-like ligands for 9 out of 20 targets.

Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach

This paper identifies and characterizes RA-0002034, a covalent inhibitor of CHIKV nsP2 protease, showing potent inhibition and selectivity against alphaviruses.

Poly ADP-Ribose Signaling is Dysregulated in Huntington Disease Patients

The paper identifies a deficient PAR response in Huntington disease patients, suggesting a potential therapeutic target for early intervention.

Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection

The paper curates a database of helicase inhibitors, Heli-SMACC, and tests selected compounds against SARS-CoV-2 NSP13 ATPase, finding twelve inhibitors with dose-response activity.

A chemical probe to modulate human GID4 Pro/N-degron interactions

The paper introduces PFI-7, a chemical probe that inhibits GID4 Pro/N-degron interactions, revealing non-degradative roles of the CTLH complex in human cells.

PRMT5 is required for full-length HTT expression by repressing multiple proximal intronic polyadenylation sites

This paper identifies PRMT5 as a regulator of HTT mRNA splicing and alternative polyadenylation, showing that its inhibition reduces full-length HTT protein levels by promoting premature termination and cleavage.

Interplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex

The paper shows that the CTLH E3 ligase complex regulates substrate selectivity and autoregulation by exchanging its β-propeller subunits WDR26 and muskelin.

Huntingtin is an RNA-binding protein and participates in NEAT1-mediated paraspeckles

This study identifies huntingtin as an RNA-binding protein that interacts with G-rich RNA sequences, including those in the NEAT1 paraspeckle lncRNA.

SETDB1 Triple Tudor Domain Ligand, (R,R)-59, Promotes Methylation of Akt1 in Cells

The paper shows that (R,R)-59, a SETDB1 ligand, enhances SETDB1-mediated methylation of Akt1 and promotes cell proliferation.

Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation

The paper designs over ten thousand {square}{beta}{beta}{square} proteins, identifies stability determinants, and demonstrates how high-throughput methods can improve protein design success rates.

LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium

This study identifies LSD1 as a repressor of a neonatal/reparative gene program in adult intestinal epithelium, showing its role in Paneth cell differentiation and regenerative capacity.

MLL1 minimal catalytic complex is a dynamic conformational ensemble susceptible to pharmacological allosteric disruption

The paper investigates the dynamic structure of the MLL1 catalytic complex and shows it can be disrupted by pharmacological agents targeting specific interaction sites.