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Catalysis of serine oligopeptidases is controlled by a gating filter mechanism.

ABSTRACT: 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 beta-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.

SUBMITTER: Fulop V

PROVIDER: S-EPMC1083722 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature

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Catalysis of serine oligopeptidases is controlled by a gating filter mechanism.

Fülöp V V Szeltner Z Z Polgár L L

EMBO reports 20000901 3

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 beta-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 ...[more]

PMID: 11256612

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