Journal Article Review Epublish 11 citations
PubMed: 38339082 DOI: 10.3390/ijms25031804
The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.
Int J Mol Sci 25(3)
Authors: Edward D Chan, Paul T King, Xiyuan Bai, Allen M Schoffstall, Robert A Sandhaus, Ashley M Buckle
Affiliations
- Department of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO 80045, USA.
- Department of Academic Affairs, National Jewish Health, Denver, CO 80206, USA.
- Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
- Medicine Monash Health, Monash University, Clayton, VIC 3800, Australia.
- Department of Chemistry and Biochemistry, University of Colorado, Colorado Springs, CO 80918, USA.
- Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
- Replay, San Diego, CA 92121, USA.
Abstract
Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: the ability to fight infections; the activation of blood coagulation or blood clot lysis systems; the activation of digestive enzymes; and reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.
MeSH
Serine Proteases, Blood, Thrombin, Antithrombin Iii, Glycosaminoglycans, Heparin, Enzymes, Fibrinolysin, Peptide Hydrolases, Protease Inhibitors, Serpins, Esterases, Serine