Related Experiment Video

Updated: May 18, 2026

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
12:07

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET

Published on: October 9, 2021

Molecular dynamics simulation of Autotaxin: roles of the nuclease-like domain and the glycan modification

Michio Koyama1, Hiroshi Nishimasu, Ryuichiro Ishitani

  • 1Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Tokyo 113-0032, Japan.

The Journal of Physical Chemistry. B
|September 13, 2012
PubMed

Insights

Molecular dynamics simulations reveal how Autotaxin's (ATX) nuclease-like domain and N-glycosylation stabilize its catalytic activity through an allosteric pathway. This finding clarifies the roles of these key structural elements in ATX function.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Autotaxin (ATX) is a secreted enzyme producing lysophosphatidic acid, a lipid mediator.
  • ATX activates G protein-coupled receptors, influencing various cellular processes.
  • The nuclease-like domain and N-glycosylation are known to be crucial for ATX catalytic activity.

Purpose of the Study:

  • To elucidate the precise roles of the nuclease-like domain and N-glycosylation in ATX catalytic activity.
  • To investigate the structural mechanisms underlying ATX function using computational methods.

Main Methods:

  • Molecular dynamics simulations of full-length ATX.
  • Simulations of ATX variants lacking the nuclease-like domain and/or N-glycosylation.
  • Analysis of structural changes and interactions within ATX.

Main Results:

  • An allosteric interaction pathway involving the catalytic domain, insertion regions, N-glycan, and nuclease-like domain was identified.
  • This pathway appears to stabilize the catalytic threonine residue's position.
  • The findings provide a structural basis for previously observed biochemical data.

Conclusions:

  • The nuclease-like domain and N-glycosylation are integral to ATX's catalytic mechanism through an allosteric network.
  • Molecular dynamics simulations offer valuable insights into enzyme structure-function relationships.
  • This study complements existing biochemical data, enhancing the understanding of Autotaxin's enzymatic function.

More Related Videos

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

Characterization of Multi-subunit Protein Complexes of Human MxA Using Non-denaturing Polyacrylamide Gel-electrophoresis08:55

Characterization of Multi-subunit Protein Complexes of Human MxA Using Non-denaturing Polyacrylamide Gel-electrophoresis

Published on: October 28, 2016

Related Concept Videos

Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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 pathway,...
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Mechanical Protein Functions01:58

Mechanical Protein Functions

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.