The Human Protease Inhibitor Cystatin C Is an Activating Cofactor for the Streptococcal Cysteine Protease IdeS
| Autor: | Ulrich von Pawel-Rammingen, Bjarne Vincents, Reine Vindebro, Magnus Abrahamson |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Proteases
MICROBIO PROTEINS medicine.medical_treatment Clinical Biochemistry Drug Evaluation Preclinical Biology urologic and male genital diseases Biochemistry Bacterial Proteins Drug Discovery medicine Humans Protease Inhibitors Cystatin C Molecular Biology reproductive and urinary physiology Pharmacology Protease Hydrolysis Streptococcus General Medicine Surface Plasmon Resonance Cystatins Cysteine protease female genital diseases and pregnancy complications Protease inhibitor (biology) Enzyme Activation NS2-3 protease Cysteine Endopeptidases Kinetics CHEMBIO Immunoglobulin G Cystatin A biology.protein Molecular Medicine Cystatin Protein Binding medicine.drug |
| Zdroj: | Chemistry & Biology. 15:960-968 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2008.07.021 |
| Popis: | SummaryHuman cystatin C is considered the physiologically most important inhibitor of endogenous papain-like cysteine proteases. We present here an unexpected function of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS of the human pathogen Streptococcus pyogenes. IdeS activity is not dependent on cystatin C, but is significantly enhanced in the presence of cystatin C. We report a protease inhibitor that accelerates the activity of its putative target protease and a unique example of how a host protease inhibitor is “hijacked” by a bacterial protease to increase its activity. This finding has important implications for the view on protease-inhibitor interactions, and is relevant to consider in the therapeutic use of protease inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|