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 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.
Fülöp
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V
Department of Biological Sciences, University of Warwick, Coventry, UK.
Szeltner
Z
Z
Polgár
L
L
D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000201:enzymology; D002384:Catalysis; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004795:Enzyme Stability; D019803:Glutathione Disulfide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D000085822:Prolyl Oligopeptidases; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013552:Swine; D013696:Temperature
D004220:Disulfides; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D003545:Cysteine; D019803:Glutathione Disulfide