Catalysis of serine oligopeptidases is controlled by a gating filter mechanism

Proteases have a variety of strategies for selecting substrates in order to prevent uncontrolled protein degradation. A recent crystal structure determination of prolyl oligopeptidase has suggested a way for substrate selection involving an unclosed seven‐bladed β‐propeller domain. We have engineere...

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Bibliographic Details
Published in:EMBO reports 2000-09, Vol.1 (3), p.277-281
Main Authors: Fülöp, Vilmos, Szeltner, Zoltán, Polgár, László
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
Biodegradation
Brain - enzymology
Catalysis
Crystallography, X-Ray
Cysteine - genetics
Cysteine - metabolism
Disulfides - chemistry
Disulfides - metabolism
Enzymatic activity
Enzyme Stability
Glutathione Disulfide - metabolism
Hydrogen-Ion Concentration
Kinetics
Models, Molecular
Mutation
Oxidation-Reduction
Protein Conformation
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Scientific Report
Scientific Reports
Serine Endopeptidases - chemistry
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Substrate Specificity
Swine
Temperature
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Summary:Proteases have a variety of strategies for selecting substrates in order to prevent uncontrolled protein degradation. A recent crystal structure determination of prolyl oligopeptidase has suggested a way for substrate selection involving an unclosed seven‐bladed β‐propeller domain. We have engineered a disulfide bond between the first and seventh blades of the propeller, which resulted in the loss of enzymatic activity. These results provided direct evidence for a novel strategy of regulation in which oscillating propeller blades act as a gating filter during catalysis, letting small peptide substrates into the active site while excluding large proteins to prevent accidental proteolysis.
ISSN:1469-221X
1469-3178
DOI:10.1093/embo-reports/kvd048