Specific inhibition of mature fungal serine proteinases and metalloproteinases by their propeptides.

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  • Additional Information
    • Source:
      Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 2985120R Publication Model: Print Cited Medium: Print ISSN: 0021-9193 (Print) Linking ISSN: 00219193 NLM ISO Abbreviation: J Bacteriol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Society for Microbiology
    • Subject Terms:
      Aspergillus fumigatus/*enzymology ; Enzyme Precursors/*pharmacology ; Metalloendopeptidases/*antagonists & inhibitors ; Protease Inhibitors/*pharmacology ; Serine Endopeptidases/*drug effects; Aspergillus fumigatus/genetics ; Base Sequence ; Dose-Response Relationship, Drug ; Enzyme Precursors/genetics ; Metalloendopeptidases/genetics ; Molecular Sequence Data ; Recombinant Fusion Proteins/pharmacology ; Serine Endopeptidases/genetics
    • Abstract:
      The function of the long propeptides of fungal proteinases is not known. Aspergillus fumigatus produces a 33-kDa serine proteinase of the subtilisin family and a 42-kDa metalloproteinase of the thermolysin family. These extracellular enzymes are synthesized as preproenzymes containing large amino-terminal propeptides. Recombinant propeptides were produced in Escherichia coli as soluble fusion proteins with glutathione S-transferase or thioredoxin and purified by affinity chromatography. A. fumigatus serine proteinase propeptide competitively inhibited serine proteinase, with a Ki of 5.3 x 10(-6) M, whereas a homologous serine proteinase from A. flavus was less strongly inhibited and subtilisin was not inhibited. Binding of metalloproteinase propeptide from A. fumigatus to the mature metalloenzyme was demonstrated. This propeptide strongly inhibited its mature enzyme, with a Ki of 3 x 10(-9) M, whereas thermolysin and a metalloproteinase from A. flavus were not inhibited by this propeptide. Enzymatically inactive metalloproteinase propeptide complex could be completely activated by trypsin treatment. These results demonstrate that the propeptides of the fungal proteinases bind specifically and inhibit the respective mature enzymes, probably reflecting a biological role of keeping these extracellular enzymes inactive until secretion.
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    • Grant Information:
      AI-30629 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Enzyme Precursors)
      0 (Protease Inhibitors)
      0 (Recombinant Fusion Proteins)
      EC 3.4.21.- (Serine Endopeptidases)
      EC 3.4.24.- (Metalloendopeptidases)
    • Publication Date:
      Date Created: 19960401 Date Completed: 19960710 Latest Revision: 20190508
    • Publication Date:
      20231215
    • Accession Number:
      PMC177927
    • Accession Number:
      10.1128/jb.178.8.2211-2215.1996
    • Accession Number:
      8636020