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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
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Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation
1From the Centenary Institute, National Health and Medical Research Council Clinical Trials Centre, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2006, Australia.
The Journal of Biological Chemistry
|January 13, 2019
Summary
Functional disulfide bonds regulate protein activity and are key targets for drug development. Understanding these allosteric disulfides is crucial for advancing therapies in areas like cancer and thrombosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Protein disulfide bonds typically serve structural roles.
- A subset of disulfide bonds, termed allosteric disulfides, dynamically regulate protein function.
- These cleavable bonds influence critical biological processes including hemostasis, immunity, and viral infection.
Purpose of the Study:
- To highlight the significance of allosteric disulfides in biological regulation.
- To discuss the emerging understanding of their facile cleavage and conformational signatures.
- To emphasize their potential as extracellular drug targets.
Main Methods:
- Identification and characterization of allosteric disulfide bonds across biological systems.
- Analysis of conformational signatures associated with these functional disulfides.
- Investigation of factors that cleave these bonds.
Main Results:
- Allosteric disulfides control protein function in mammals, impacting hemostasis, immune response, and viral infection.
- A conformational signature aids in identifying these functional disulfide bonds.
- Extracellular cleavage of these bonds presents opportunities for therapeutic intervention.
Conclusions:
- Allosteric disulfides represent a sophisticated regulatory mechanism for protein function.
- Their extracellular location makes them attractive drug targets, with inhibitors already in clinical trials.
- Further development of tools and techniques is needed to fully exploit their therapeutic potential.
Keywords:
disulfideprotein chemistryprotein conformationprotein dynamicprotein disulfide isomerasedrug discoveryoxidation-reduction (redox)post-translational modificationprotein chemical modificationthiolallostericcysteinecystinedisulfide bondoxidoreductaseMore Related Videos
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