Startseite Characterization of PdCP1, a serine carboxypeptidase from Pseudogymnoascus destructans, the causal agent of White-nose Syndrome
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Characterization of PdCP1, a serine carboxypeptidase from Pseudogymnoascus destructans, the causal agent of White-nose Syndrome

  • Chapman Beekman , Zhenze Jiang , Brian M. Suzuki , Jonathan M. Palmer , Daniel L. Lindner , Anthony J. O’Donoghue , Giselle M. Knudsen und Richard J. Bennett ORCID logo EMAIL logo
Veröffentlicht/Copyright: 26. Oktober 2018
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 399 Heft 12

Abstract

Pseudogymnoascus destructans is a pathogenic fungus responsible for White-nose Syndrome (WNS), a disease afflicting multiple species of North American bats. Pseudogymnoascus destructans infects susceptible bats during hibernation, invading dermal tissue and causing extensive tissue damage. In contrast, other Pseudogymnoascus species are non-pathogenic and cross-species comparisons may therefore reveal factors that contribute to virulence. In this study, we compared the secretome of P. destructans with that from several closely related Pseudogymnoascus species. A diverse set of hydrolytic enzymes were identified, including a putative serine peptidase, PdCP1, that was unique to the P. destructans secretome. A recombinant form of PdCP1 was purified and substrate preference determined using a multiplexed-substrate profiling method based on enzymatic degradation of a synthetic peptide library and analysis by mass spectrometry. Most peptide substrates were sequentially truncated from the carboxyl-terminus revealing that this enzyme is a bona fide carboxypeptidase. Peptides with arginine located close to the carboxyl-terminus were rapidly cleaved, and a fluorescent substrate containing arginine was therefore used to characterize PdCP1 activity and to screen a selection of peptidase inhibitors. Antipain and leupeptin were found to be the most potent inhibitors of PdCP1 activity.

Keywords: bat infection; peptidase; proteomics; secretome; virulence

Funding source: National Science Foundation

Award Identifier / Grant number: NSF-1456787

Funding statement: We thank Matt Ravalin for his advice on inhibitors of PdCP1. Funding for this project was provided by a National Science Foundation, Funder ID (10.13039/100000001), grant (NSF-1456787) to R.J.B. and Skaggs School of Pharmacy and Pharmacutical Sciences to A.J.O. Funding for J.M.P. and D.L.L. was provided by the Northern Research Station, USDA Forest Service. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0240).

Received: 2018-05-01
Accepted: 2018-09-24
Published Online: 2018-10-26
Published in Print: 2018-11-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Frontiers in Proteolysis
  3. Host cell-surface proteins as substrates of gingipains, the main proteases of Porphyromonas gingivalis
  4. A single domain antibody against the Cys- and His-rich domain of PCSK9 and evolocumab exhibit different inhibition mechanisms in humanized PCSK9 mice
  5. Characterization of PdCP1, a serine carboxypeptidase from Pseudogymnoascus destructans, the causal agent of White-nose Syndrome
  6. An internally quenched peptide as a new model substrate for rhomboid intramembrane proteases
  7. An alternative processing pathway of APP reveals two distinct cleavage modes for rhomboid protease RHBDL4
  8. Reviews
  9. Salivary peptide histatin 1 mediated cell adhesion: a possible role in mesenchymal-epithelial transition and in pathologies
  10. Modulation of dynamin function by small molecules
  11. Chemotherapeutic resistance: a nano-mechanical point of view
  12. Research Articles/Short Communications
  13. Protein Structure and Function
  14. Biochemical and kinetic properties of the complex Roco G-protein cycle
  15. Cell Biology and Signaling
  16. Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis
https://doi.org/10.1515/hsz-2018-0240
Schlagwörter für diesen Artikel
bat infection; peptidase; proteomics; secretome; virulence

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Frontiers in Proteolysis
  3. Host cell-surface proteins as substrates of gingipains, the main proteases of Porphyromonas gingivalis
  4. A single domain antibody against the Cys- and His-rich domain of PCSK9 and evolocumab exhibit different inhibition mechanisms in humanized PCSK9 mice
  5. Characterization of PdCP1, a serine carboxypeptidase from Pseudogymnoascus destructans, the causal agent of White-nose Syndrome
  6. An internally quenched peptide as a new model substrate for rhomboid intramembrane proteases
  7. An alternative processing pathway of APP reveals two distinct cleavage modes for rhomboid protease RHBDL4
  8. Reviews
  9. Salivary peptide histatin 1 mediated cell adhesion: a possible role in mesenchymal-epithelial transition and in pathologies
  10. Modulation of dynamin function by small molecules
  11. Chemotherapeutic resistance: a nano-mechanical point of view
  12. Research Articles/Short Communications
  13. Protein Structure and Function
  14. Biochemical and kinetic properties of the complex Roco G-protein cycle
  15. Cell Biology and Signaling
  16. Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis
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