Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Enzyme Inhibition

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Benchmarking Quantum Mechanical Levels of Theory for Valence Parametrization in Force Fields.

The journal of physical chemistry. B·2024

Same author

The Open Force Field Initiative: Open Software and Open Science for Molecular Modeling.

The journal of physical chemistry. B·2024

Same author

Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.

Journal of chemical theory and computation·2023

Same author

Open Force Field BespokeFit: Automating Bespoke Torsion Parametrization at Scale.

Journal of chemical information and modeling·2022

Same author

Genomic patterns of transcription-replication interactions in mouse primary B cells.

Nucleic acids research·2022

Same author

Development and Benchmarking of Open Force Field v1.0.0-the Parsley Small-Molecule Force Field.

Journal of chemical theory and computation·2021

Same journal

Macromolecular crowding inhibits degradation of alpha-synuclein amyloid fibrils induced by cathepsins and MMP9.

Protein science : a publication of the Protein Society·2026

Same journal

Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.

Protein science : a publication of the Protein Society·2026

Same journal

The phospholipid biosynthesis enzyme PlsB contains three distinct domains for membrane association, lysophosphatidic acid synthesis, and dimerization.

Protein science : a publication of the Protein Society·2026

Same journal

Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.

Protein science : a publication of the Protein Society·2026

Same journal

Achieving protease substrate-specific inhibition by mAb dual functional selections.

Protein science : a publication of the Protein Society·2026

Same journal

How important are quantum mechanical effects in controlling biological functions: Enzymes, electron transfer and bird navigation.

Protein science : a publication of the Protein Society·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Apr 8, 2026

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity

Published on: March 25, 2020

Engineering trypsin for inhibitor resistance.

Anna R Batt¹, Commodore P St Germain¹, Trevor Gokey¹

¹Department of Chemistry & Biochemistry, San Francisco State University, San Francisco, California, 94132.

Protein Science : a Publication of the Protein Society

|June 25, 2015

Summary

This summary is machine-generated.

Developing protease therapeutics requires overcoming natural inhibitors. Key residues like Y39 and K60 in trypsin-fold proteases significantly influence inhibitor binding, guiding future drug design.

Keywords:

inhibitors molecular dynamics protein engineering serine proteases serpins trypsin

More Related Videos

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Published on: August 8, 2016

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

Related Experiment Videos

Last Updated: Apr 8, 2026

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity

Published on: March 25, 2020

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Published on: August 8, 2016

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

Area of Science:

Biochemistry
Structural Biology
Drug Discovery

Background:

Effective protease therapeutics must resist natural inhibitors while retaining activity.
Understanding protease-inhibitor interactions is crucial for developing resistant drugs.
Trypsin is a model system for studying trypsin-fold proteases, common in therapeutics.

Purpose of the Study:

To investigate the role of specific residues (Y39, K60) in trypsin's interaction with inhibitors.
To assess how mutations at these positions affect catalytic activity and inhibitor sensitivity.
To elucidate the molecular basis of inhibitor binding using computational simulations.

Main Methods:

Site-directed mutagenesis to create trypsin variants (Y39A, Y39F, K60A, K60V).
Biochemical assays to measure catalytic activity and sensitivity to inhibitors (BPTI, ecotin).
Molecular dynamics simulations to calculate binding free energies and analyze structural changes.

Main Results:

All variants maintained catalytic activity against peptide substrates.
K60A/K60V variants showed altered sensitivity to BPTI and ecotin.
Y39A and Y39F variants exhibited differential sensitivity to inhibitors, with Y39F showing the lowest binding energy to BPTI.
Molecular dynamics revealed conformational changes and new hydrogen bond formation in the Y39F variant.

Conclusions:

Residues Y39 and K60 are critical determinants of inhibitor binding in trypsin.
Mutations at these positions can modulate protease sensitivity to inhibitors.
Findings provide insights into designing protease-fold inhibitors with improved resistance profiles.