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Updated: Jul 6, 2026
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains
Alexandr P Kornev1, Susan S Taylor, Lynn F Ten Eyck
1San Diego Supercomputer Center, University of California San Diego, La Jolla, California, United States of America.
Plos Computational Biology
|April 12, 2008
Summary
Cyclic nucleotide binding domains (CNBs) have conserved structural motifs crucial for intracellular processes. This study identifies novel motifs, revealing distinct allosteric mechanisms in cis- and trans-regulated CNB domains.
Area of Science:
- Molecular biology
- Structural biology
- Bioinformatics
Background:
- Cyclic nucleotides like cAMP and cGMP are vital intracellular regulators.
- Understanding cyclic nucleotide binding (CNB) domain allostery is key for molecular and structural biologists.
Purpose of the Study:
- To investigate the allosteric mechanism of various CNB domains.
- To compare cAMP-bound and cAMP-free structures using a novel bioinformatics approach.
Main Methods:
- Local spatial pattern alignment was employed to compare protein structures.
- Analysis focused on cyclic nucleotide binding (CNB) domains, including PKA, Epac, and ionic channels.
Main Results:
- Four conserved structural motifs were identified: phosphate binding cassette (PBC), hinge, beta(2,3) loop, and the novel N3A-motif.
- The N3A-motif is characteristic of cis-regulated CNB domains, differentiating them from trans-regulated domains like CAP.
- A novel model for allosteric mechanisms in cis-regulated CNB domains was proposed.
Conclusions:
- The beta(2,3) loop and N3A-motif are newly defined conserved elements in CNB domains.
- Distinct allosteric mechanisms exist between cis-regulated (N3A-motif present) and trans-regulated (N3A-motif absent) CNB domains.
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