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Catalysis of serine oligopeptidases is controlled by a gating filter mechanism
Author(s) -
Fülöp Vilmos,
Szeltner Zoltán,
Polgár László
Publication year - 2000
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvd048
Subject(s) - proteolysis , chemistry , proteases , filter (signal processing) , serine , oligopeptidase , mechanism (biology) , biochemistry , enzyme , computer science , physics , quantum mechanics , computer vision
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.