Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

5.8K
Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
Induced-fit Model01:13

Induced-fit Model

80.9K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
80.9K
Catalytically Perfect Enzymes01:07

Catalytically Perfect Enzymes

4.0K
The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
 
Most enzymes...
4.0K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K

You might also read

Related Articles

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

Sort by
Same author

Rare coding variant architecture and gene discovery from 130,000 sequenced cases of atrial fibrillation.

Research square·2026
Same author

Rhegmatogenous Retinal Detachment Associated with Giant Retinal Tears: The Effect of Tamponade Choice on Outcome.

Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde·2026
Same author

Evaluating the Effectiveness of a Creative Arts and Philosophical Inquiry Intervention Rooted in Self-Determination Theory to Promote Adaptive Coping with Eco-Anxiety among Elementary School Children: A Pilot Randomized Cluster Trial.

Chronic stress (Thousand Oaks, Calif.)·2026
Same author

Establishment, Implementation, and Impacts of the Observatory on Student Mental Health in Higher Education in Quebec, Canada: Protocol for a Mixed Methods Research Program.

JMIR research protocols·2026
Same author

A chikungunya virus-like particle vaccine reduces chikungunya disease in cynomolgus macaques and protection is mediated by antibody transferred from vaccinated humans.

NPJ vaccines·2026
Same author

How Do Children Think About Death? A Narrative Review of Historical and Recent Developmental Perspectives Examining Children's Understanding of Death.

Clinical child psychology and psychiatry·2026
Same journal

Gasdermin E: Bridging Pyroptosis, Immunity, and Disease Pathogenesis Toward Precision Intervention.

The protein journal·2026
Same journal

Identification of Moonlighting Proteins from Published Literature Using Natural Language Processing and AI.

The protein journal·2026
Same journal

Benjamin Widom (1930-2024) and the "∫" : Physical Chemist, Theorist, and Mentor.

The protein journal·2026
Same journal

Comparison of Immunogenicity of Cood-Cotd, CfaB-st-CfaE, and Cssa-Cssb-ltb Chimeric Proteins and Their Chitosan Nanoparticles Against ETEC in an Animal Model.

The protein journal·2026
Same journal

Integrated Experimental and In-Silico Analysis Indicates Melittin as a Modulator of IL-37a-Associated Networks in Neuroblastoma.

The protein journal·2026
Same journal

Correction: In Memory of Prof. Alan George Marshall.

The protein journal·2026
See all related articles

Related Experiment Video

Updated: Jul 9, 2025

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity
07:46

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity

Published on: October 8, 2018

7.0K

An ITPA Enzyme with Improved Substrate Selectivity.

Nicholas E Burgis1, Kandise VanWormer2, Devin Robbins2

  • 1Department of Chemistry, Biochemistry & Physics, Eastern Washington University, Cheney, WA, 99004, USA. nburgis@ewu.edu.

The Protein Journal
|December 8, 2023
PubMed
Summary
This summary is machine-generated.

Infant ITPA deficiencies can be lethal. Researchers engineered a novel E22D ITPA enzyme with enhanced activity, offering a potential platform for developing new therapies for ITPA-related disorders.

Keywords:
DEE 35ITPITPAInosineRibavirinThiopurine

More Related Videos

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System
08:10

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

Published on: August 8, 2016

8.8K
Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors
09:11

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Published on: November 23, 2019

6.7K

Related Experiment Videos

Last Updated: Jul 9, 2025

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity
07:46

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity

Published on: October 8, 2018

7.0K
Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System
08:10

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

Published on: August 8, 2016

8.8K
Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors
09:11

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Published on: November 23, 2019

6.7K

Area of Science:

  • Biochemistry
  • Genetics
  • Enzyme Engineering

Background:

  • Infant deficiencies in inosine triphosphate pyrophosphatase (ITPA) can be lethal, highlighting its critical but poorly understood role in neural development.
  • ITPA gene polymorphism affects patient outcomes with ribavirin and thiopurine therapies, impacting nearly one-third of the human population.
  • Previous studies identified an E22A ITPA mutant with enhanced ITP hydrolysis activity via site-directed mutagenesis.

Purpose of the Study:

  • To investigate the biochemical properties of ITPA mutants at position 22 through rational enzyme engineering.
  • To develop an improved ITPA enzyme with enhanced substrate selectivity for therapeutic applications.

Main Methods:

  • Rational enzyme engineering of the ITPA substrate selectivity pocket at position 22.
  • Biochemical characterization of engineered ITPA mutants, including substrate selectivity assays.
  • Assessment of biological activity of the novel E22D ITPA mutant.

Main Results:

  • The E22D ITPA mutant demonstrated a two-fold improved substrate selectivity for ITP over ATP.
  • The E22D ITPA mutant showed a four-fold improved substrate selectivity for ITP over GTP.
  • The engineered E22D ITPA maintained its biological activity while exhibiting enhanced ITP hydrolysis.

Conclusions:

  • The novel E22D ITPA mutant exhibits significantly enhanced substrate selectivity and retains biological activity.
  • Engineered ITPA variants like E22D ITPA represent a promising platform for developing novel therapeutic strategies.
  • Further development of E22D ITPA could lead to improved treatments for ITPA deficiencies and related conditions.