Protease and Inhibitor Mechanisms

Thermodynamics and selection of the plasminogen activator inhibitor-1 latency transition

This study uses deep mutational scanning to analyze how PAI-1 variants affect its latency transition and uPA inhibition, showing that thermodynamic stability and evolution shape its function.

Cell-line specific role of Cathepsin B in triple-negative breast cancer growth, invasion and response to chemotherapy

This study examines the cell-line specific role of CTSB in TNBC, finding that its knockout affects viability, invasion, and chemotherapy response differently in MDA-MB-231 and MDA-MB-468 cells.

Cigarette smoking upregulates vascular expression of the novel atherosclerosis risk factor ADAMTS-7

This study shows cigarette smoke increases vascular ADAMTS7 expression through CCL17-CCR4 signaling, linking smoking to atherosclerosis via a novel gene-environment interaction.

Cryo-EM structure of CLCA1 identifies CLCA1 as a founding member of a novel metzincin family.

The paper determines the Cryo-EM structure of CLCA1, revealing its unique domain organization and regulatory mechanisms, and identifies it as a founding member of a new metzincin family.

Reverse Proteolysis Uncovers a Hidden Dimension of the Peptidome

This paper demonstrates that lysosomal cysteine cathepsins can generate fusion peptides through reverse proteolysis, revealing a new dimension of protease activity and peptide diversification.

Legumain drives processing of cathepsins and nuclear localisation of cathepsin L

This study investigates the relationship between legumain and cathepsins, showing legumain is required for cathepsin processing and nuclear localization of cathepsin L, with implications for cell proliferation and other nuclear functions.

Select azo compounds post-translationally modulate HTRA1 abundance and activity potentially through interactions at the trimer interface

This paper identifies specific azo compounds that enhance HTRA1 abundance but have varying effects on its activity, suggesting potential therapeutic applications for diseases like AMD.

Structural Insights into the Activation and Inhibition of the ADAM17-iRhom2 Complex

The paper presents the cryo-EM structure of the ADAM17-iRhom2 complex, elucidates its inhibitory mechanisms, and validates findings with cellular assays.

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.

Conformational and Functional Regulation of SET by Legumain Cleavage

This study shows legumain cleaves SET at two sites, forming a stable complex and impairing its interaction with histone 1, while also abolishing SET's positive modulation of PP2A activity.

The protease ADAMTS5 controls ovarian cancer cell invasion, downstream of Rab25.

This study shows ADAMTS5 promotes ovarian cancer cell invasion via Rab25 and NF-κB signaling, with high ADAMTS5 expression linked to poor patient prognosis.

High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases

This study uses deep mutational scanning to analyze PAI-1's inhibitory interactions with three serine proteases, revealing sequence determinants and evolutionary conservation of specificity.

Effect of TIMPs and Their Minimally Engineered Variants in Blocking Invasion and Migration of Brain Cancer Cells

This study evaluates engineered TIMP variants to inhibit MMP activity in GBM cells, showing their potential to reduce tumor invasion and migration.

Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency

This study identifies low nanomolar TMPRSS13 inhibitors through chemical library screening and molecular modeling, showing their ability to block SARS-CoV-2 pseudovirus entry.

The substrate changes matrix metalloprotease-1 dynamics, allostery, and ligand binding affinity

This paper shows collagen affects MMP1 dynamics, allostery, and ligand binding through MD simulations and virtual screening, revealing substrate-specific allosteric residues and potential drug targets.

An in vitro platform for the enzymatic characterization of the rhomboid protease RHBDL4

This study characterizes RHBDL4 enzymatic properties using an in vitro platform, identifying effective inhibitors and providing insights for drug development.

Deciphering Features of Metalloprotease Cleavage Targets Using Protein Structure Prediction

The paper identifies structural features of ADAM10 cleavage substrates using protein structure prediction and develops a classification algorithm to predict cleavage sites.

Profiling endogenous airway proteases and antiproteases and measuring proteolytic activation of Influenza HA using in vitro and ex vivo human airway surface liquid samples

This study profiles airway proteases and antiproteases in human samples and measures proteolytic activation of viral proteins, finding significant differences in cleavage rates between smokers and non-smokers.

Comprehensive protease specificity profiling

This study presents a method to comprehensively profile protease cleavage specificity using in vitro selection, high-throughput sequencing, and mass spectrometry, revealing extended spectrum preferences for broad specificity proteases.

Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension

This study extends the plasma half-life of N-TIMP2 by appending a PATylated tail, showing improved therapeutic potential in mice.

SERPINA11 related novel Serpinopathy- a perinatal lethal disorder

The paper identifies a perinatal lethal disorder caused by biallelic loss-of-function variants in SERPINA11, showing its role in extracellular matrix remodelling during embryonic development.

The novel coronary artery disease risk factor ADAMTS-7 modulates atherosclerotic plaque formation by degradation of TIMP-1

This study identifies ADAMTS-7 as a risk factor for atherosclerosis by degrading TIMP-1, reducing its inhibition of MMP-9 and promoting collagen degradation.

The ADAM17 sheddase complex regulator iTAP modulates inflammation, epithelial repair, and tumor growth

This study shows that iTAP regulates ADAM17 activity, affecting inflammation, epithelial repair, and tumor growth in mice without causing widespread ADAM17 loss effects.

Protease Activity Analysis: A Toolkit for Analyzing Enzyme Activity Data

The paper introduces PAA, a toolkit for analyzing protease activity data, offering preprocessing, visualization, and machine learning tools to standardize analysis across in vitro and in vivo assays.

The conserved, secreted protease inhibitor MLT-11 is necessary for C. elegans molting and embryogenesis

This study identifies MLT-11, a protease inhibitor essential for C. elegans molting and embryogenesis, showing its role in aECM remodeling and cuticle integrity.

Uncovering the evolutionary tail of GZMM: An NSP4 related protease

This study investigates the evolutionary relationship between NSP4 and GZMM, finding a closer evolutionary link between Prss57/NSP4 and Gzmm/GZMM than with other proteases.

An unexpected role for the conserved ADAM-family metalloprotease ADM-2 in Caenorhabditis elegans molting

This paper identifies ADM-2 as a negative regulator of molting in C. elegans, showing it inhibits molting by regulating LRP-1 and endocytic trafficking.

TAILS identifies candidate substrates and biomarkers of ADAMTS7, a therapeutic protease target in coronary artery disease

The paper identifies ADAMTS7 substrates and cleavage sites using TAILS, revealing potential biomarkers for coronary artery disease.

A comprehensive phylogenetic analysis of the serpin superfamily

This study constructs a comprehensive phylogeny of 6000 serpin sequences across all kingdoms of life, showing convergent evolution rather than horizontal gene transfer for the central hub proteins.

Exploring the Landscape of Ectodomain Shedding by Quantitative Protein Terminomics

The paper identifies cleavage sites of ectodomain shedding in 10 human cell lines using mass spectrometry and finds 411 cleavage sites on 132 membrane proteins.