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Mechanism of action of a Janus-faced single-domain proteininhibitor simultaneously targeting two peptidase classes
- Source :
- Chem. Sci., Digital.CSIC. Repositorio Institucional del CSIC, instname, Chem. Sci.; Vol 4
- Publication Year :
- 2013
-
Abstract
- Protein inhibitors provide a physiological mechanism for the regulation of proteolytic enzymes. While most single-domain inhibitors have one reactive site with which they target peptidases of a specific catalytic class, selected specimens inhibit two peptidase molecules simultaneously, thus giving rise to ternary complexes. To study such inhibition, we analyzed the function of one of these proteins, sermetstatin, which strongly binds as a dimer to serine proteinases (SPs) and a metallopeptidase (MP). In addition, we determined the structures of the isolated inhibitor dimer and its heterotetrameric complexes with the SP subtilisin and the MP snapalysin, which reveal that inhibition occurs through two independent distal reactive sites. These structures and the derived model for the heterohexameric complex provide for the first time a detailed view of the molecular mechanism of simultaneous inhibition of proteinases belonging to two distinct mechanistic classes by a single-domain protein. © The Royal Society of Chemistry 2013.
- Subjects :
- 0303 health sciences
Metallopeptidase
Proteinase inhibitor
Stereochemistry
Dimer
030302 biochemistry & molecular biology
Proteolytic enzymes
Subtilisin
General Chemistry
Biology
03 medical and health sciences
chemistry.chemical_compound
Mechanism of action
Biochemistry
chemistry
medicine
Molecule
medicine.symptom
Function (biology)
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 20416539 and 20416520
- Volume :
- 4
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Chem. Sci.
- Accession number :
- edsair.doi.dedup.....b58f9db4081a33b8b28e5f0612a6ebca
- Full Text :
- https://doi.org/10.1039/C2SC21712K