Matt Coban
YOU?
Author Swipe
View article: Modifying inhibitor specificity for homologous enzymes by machine learning
Modifying inhibitor specificity for homologous enzymes by machine learning Open
Selective inhibitors are essential for targeted therapeutics and for probing enzyme functions in various biological systems. The two main challenges in identifying such protein‐based inhibitors lie in the extensive experimental effort requ…
View article: Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition
Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition Open
Selective inhibition of the more than 100 S1 family serine proteases is a long-standing challenge due to their active site similarity. Mesotrypsin, implicated in cancer progression, exemplifies these difficulties; no current inhibitors ach…
View article: Directed evolution of metalloproteinase inhibitor TIMP-1 for selective inhibition of MMP-9 exploits catalytic and fibronectin domain interactions
Directed evolution of metalloproteinase inhibitor TIMP-1 for selective inhibition of MMP-9 exploits catalytic and fibronectin domain interactions Open
Matrix metalloproteinase-9 (MMP-9) is a critical enzyme involved in extracellular matrix degradation and is strongly implicated in many diseases, including triple-negative breast cancer and other poor prognosis cancers. Selective inhibitio…
View article: Dynamicasome! Comprehensive Mutational Analysis and AI-Driven Prediction of PMM2 Pathogenicity: Integrating Molecular Dynamics Simulations with Machine Learning Models
Dynamicasome! Comprehensive Mutational Analysis and AI-Driven Prediction of PMM2 Pathogenicity: Integrating Molecular Dynamics Simulations with Machine Learning Models Open
Advances in genomic medicine have accelerated the identification of mutations in disease- associated genes, but the pathogenicity of many mutations remains unknown, hindering their use in diagnostics and clinical decision-making. Predictiv…
View article: Targeting Invasion: The Role of MMP-2 and MMP-9 Inhibition in Colorectal Cancer Therapy
Targeting Invasion: The Role of MMP-2 and MMP-9 Inhibition in Colorectal Cancer Therapy Open
Colorectal cancer (CRC) remains one of the most prevalent and lethal cancers worldwide, prompting ongoing research into innovative therapeutic strategies. This review aims to systematically evaluate the role of gelatinases, specifically MM…
View article: Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension
Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension Open
Matrix metalloproteinases (MMPs) are significant drivers of many diseases, including cancer, and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous MMP inhibitors and are being purs…
View article: Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W
Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W Open
Mutations in the PINK1 and PRKN genes are the most frequent genetic cause of early-onset Parkinson disease. The pathogenic p.R275W substitution in PRKN is the most frequent substitution observed in patients, and thus far has been character…
View article: Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension
Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension Open
Matrix Metalloproteinases (MMPs) are drivers of many diseases including cancer and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are human proteins that inhibit MMPs and are being pursued for…
View article: In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling
In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling Open
Complete loss-of-function mutations in the PRKN gene are a major cause of early-onset Parkinson’s disease (PD). PRKN encodes the Parkin protein, an E3 ubiquitin ligase that works in conjunction with the ubiquitin kinase PINK1 in a distinct…
View article: Abstract 1331 Engineering Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Variants with Improved Binding Selectivity toward Matrix Metalloproteinase-9 (MMP-9) as potential protein therapeutics
Abstract 1331 Engineering Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Variants with Improved Binding Selectivity toward Matrix Metalloproteinase-9 (MMP-9) as potential protein therapeutics Open
Introduction:Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the function and activity of matrix metalloproteinases (MMPs), enzymes that are known for their involvement in cancer progression. TIMPs p…
View article: Abstract 1915 Allosteric inhibition of serine proteases: a case study with the pro-oncogenic enzyme mesotrypsin
Abstract 1915 Allosteric inhibition of serine proteases: a case study with the pro-oncogenic enzyme mesotrypsin Open
Mesotrypsin is an S1 family serine protease which promotes invasiveness of several human cancers. Other S1 family members play important roles in digestion, coagulation, and other critical biological processes. The active sites of these en…
View article: Abstract 1734 Investigating the catalytic activity of PRSS23 as a novel serine protease in ovarian cancer
Abstract 1734 Investigating the catalytic activity of PRSS23 as a novel serine protease in ovarian cancer Open
Introduction: Proteases play important roles in regulating protein activity and turnover, while their dysregulation can lead to disease. Among the >600 human proteases, many still lack defined functions. Serine Protease 23 (PRSS23) is a pu…
View article: Abstract 1954 Deciphering Selectivity in Mesotrypsin Inhibition: Validating an allosteric mechanism through mutation and enzyme kinetics
Abstract 1954 Deciphering Selectivity in Mesotrypsin Inhibition: Validating an allosteric mechanism through mutation and enzyme kinetics Open
Introduction: Mesotrypsin, a significant member of the S1 serine protease family, is increasingly recognized for its role in the progression of cancers, particularly in the prostate and lung. Our research aims to develop selective and pote…
View article: Structure and computation-guided yeast surface display for the evolution of TIMP-based matrix metalloproteinase inhibitors
Structure and computation-guided yeast surface display for the evolution of TIMP-based matrix metalloproteinase inhibitors Open
The study of protein-protein interactions (PPIs) and the engineering of protein-based inhibitors often employ two distinct strategies. One approach leverages the power of combinatorial libraries, displaying large ensembles of mutant protei…
View article: Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant
Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant Open
(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cy…
View article: Novel NFkB Variant V213E: Phenotypic Description & Molecular Modeling
Novel NFkB Variant V213E: Phenotypic Description & Molecular Modeling Open
BACKGROUND Mutations of NFkB1 are a known cause of inborn errors of immunity resulting in immunodeficiency due to the role of NFkB1 as a transcriptional regulator of immunomodulating proteins. We present a patient with a diagnosis of commo…
View article: Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14
Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14 Open
Matrix metalloproteinases (MMPs) regulate the degradation of extracellular matrix (ECM) components in biological processes. MMP activity is controlled by natural tissue inhibitors of metalloproteinases (TIMPs) that non-selectively inhibit …
View article: Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14
Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14 Open
Matrix metalloproteinases (MMPs) regulate the degradation of extracellular matrix (ECM) components in biological processes. MMP activity is controlled by natural tissue inhibitors of metalloproteinases (TIMPs) that non-selectively inhibit …
View article: Substitution of PINK1 Gly411 modulates substrate receptivity and turnover
Substitution of PINK1 Gly411 modulates substrate receptivity and turnover Open
The ubiquitin (Ub) kinase-ligase pair PINK1-PRKN mediates the degradation of damaged mitochondria by macroautophagy/autophagy (mitophagy). PINK1 surveils mitochondria and upon stress accumulates on the mitochondrial surface where it phosph…
View article: Activity-based protein profiling reveals active serine proteases that drive malignancy of human ovarian clear cell carcinoma
Activity-based protein profiling reveals active serine proteases that drive malignancy of human ovarian clear cell carcinoma Open
Ovarian clear cell carcinoma (OCCC) is an understudied poor prognosis subtype of ovarian cancer lacking in effective targeted therapies. Efforts to define molecular drivers of OCCC malignancy may lead to new therapeutic targets and approac…
View article: Substitution of PINK1 Gly411 modulates substrate receptivity and turnover
Substitution of PINK1 Gly411 modulates substrate receptivity and turnover Open
The ubiquitin (Ub) kinase-ligase pair PINK1-PRKN mediates the degradation of damaged mitochondria by macroautophagy/autophagy (mitophagy). PINK1 surveils mitochondria and upon stress accumulates on the mitochondrial surface where it phosph…
View article: Substitution of PINK1 Gly411 modulates substrate receptivity and turnover
Substitution of PINK1 Gly411 modulates substrate receptivity and turnover Open
The ubiquitin (Ub) kinase-ligase pair PINK1-PRKN mediates the degradation of damaged mitochondria by macroautophagy/autophagy (mitophagy). PINK1 surveils mitochondria and upon stress accumulates on the mitochondrial surface where it phosph…
View article: A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor
A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor Open
Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetr…