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 Experiment Videos

A molecular model for interfacial activation in phospholipase A2

J Warwicker1

  • 1Food Macromolecular Science Department, Institute of Food Research, Reading Laboratory, UK. james.warwicker@bbsrc.ac.uk

FEBS Letters
|March 10, 1997
PubMed
Summary

Electrostatic calculations reveal that amino-terminal conformation and ionization are key to phospholipase A2 transition state stability. This suggests a mechanism for interfacial activation, where substrate binding controls these factors.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues.

American journal of physiology. Cell physiology·2016
Same author

Specific ion and buffer effects on protein-protein interactions of a monoclonal antibody.

Molecular pharmaceutics·2014
Same author

The role of electrostatics in protein-protein interactions of a monoclonal antibody.

Molecular pharmaceutics·2014
Same author

Freezing and folding behavior in simple off-lattice heteropolymers.

The Journal of chemical physics·2004
Same author

Biochemical and genetic evidence for a family of heterotrimeric G-proteins in Trichomonas vaginalis.

Molecular and biochemical parasitology·2003
Same author

A second eIF4E protein in Schizosaccharomyces pombe has distinct eIF4G-binding properties.

Nucleic acids research·2001

Area of Science:

  • Biochemistry
  • Computational Chemistry
  • Enzyme Kinetics

Background:

  • Phospholipase A2 (PLA2) enzymes are crucial in biological membranes.
  • Interfacial activation is a hallmark of many PLA2 enzymes, but its molecular basis is not fully understood.
  • The role of the enzyme's amino-terminus in catalytic activity and activation is an area of ongoing research.

Purpose of the Study:

  • To investigate the electrostatic contributions of the amino-terminal region to the catalytic mechanism of phospholipase A2.
  • To explore the role of amino-terminal conformation and ionization in transition state stability.
  • To propose a mechanism for interfacial activation based on electrostatic principles and substrate binding.

Main Methods:

  • Utilized electrostatic calculations to model the interactions within the phospholipase A2 active site.

Related Experiment Videos

  • Simulated the effects of amino-terminal conformation and ionization on transition state stability.
  • Analyzed the influence of interface charge and the structure of the interfacial complex on catalytic activity.

    • Main Results:

    • Electrostatic calculations predict significant contributions of amino-terminal conformation and ionization to transition state stability.
    • A model is proposed where binding to aggregated substrate controls these amino-terminal factors, explaining interfacial activation.
    • Transient deprotonation of an ordered amino-terminus is suggested as a source of pH dependence in interfacial activity.
    • Interface charge and the detailed structure of the interfacial complex are predicted to modulate catalytic activity.

    Conclusions:

    • The amino-terminus of phospholipase A2 plays a critical role in catalytic activity and interfacial activation through electrostatic effects.
    • Substrate binding at interfaces likely modulates the amino-terminus to enhance catalysis.
    • The findings provide a plausible electrostatic model for phospholipase A2 interfacial activation, consistent with existing biochemical data.