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09:47
The Determination of Protease Specificity in Mouse Tissue Extracts by MALDI-TOF Mass Spectrometry: Manipulating PH to Cause Specificity Changes
Published on: May 25, 2018
Exosite determinants of serpin specificity.
Peter G W Gettins1, Steven T Olson
1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60612, USA. pgettins@uic.edu
The Journal of Biological Chemistry
|April 30, 2009
Summary
Human serpins use exosites to achieve specific proteinase inhibition, often down-regulating activity until cofactor engagement. This review explores how exosites fine-tune serpin specificity in vital pathways like blood coagulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Serpins are large protein families regulating proteolytic pathways.
- Many serpins act as suicide inhibitors of serine and cysteine proteinases.
- Redundancy in primary specificity is overcome by exosites for precise targeting.
Purpose of the Study:
- To review the role of exosites in human serpin specificity.
- To examine how exosites modulate interactions in binary and ternary complexes.
- To explore indirect effects of exosites on proteolytic processes.
Main Methods:
- Review of literature on human serpins and their exosites.
- Analysis of nine specific human serpins utilizing exosites.
- Examination of cofactor-dependent mechanisms.
Main Results:
- Exosites are crucial for achieving high specificity in serpin-proteinase interactions.
- Engagement of exosites often regulates and down-regulates inhibitory activity.
- Maspin and plasminogen activator inhibitor-1 use exosites to indirectly influence proteolysis.
Conclusions:
- Exosite engagement is a key mechanism for fine-tuning serpin function.
- Serpin specificity relies on a combination of primary sites and exosites.
- Understanding exosite function is vital for comprehending proteolytic pathway regulation.
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