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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 399, Issue 12


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

Chapman Beekman
  • Department of Molecular Microbiology and Immunology, Brown University, 171 Meeting Street, Providence, RI 02912, USA
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/ Zhenze Jiang
  • Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
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/ Brian M. Suzuki
  • Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
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/ Jonathan M. Palmer
  • Center for Forest Mycology Research, Northern Research Station, USDA Forest Service, Madison, WI, USA
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/ Daniel L. Lindner
  • Center for Forest Mycology Research, Northern Research Station, USDA Forest Service, Madison, WI, USA
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/ Anthony J. O’Donoghue
  • Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
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/ Giselle M. Knudsen
  • Alaunus Biosciences, Inc., San Francisco, CA, USA
  • Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA
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/ Richard J. BennettORCID iD: http://orcid.org/0000-0002-3277-9827
Published Online: 2018-10-26 | DOI: https://doi.org/10.1515/hsz-2018-0240


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.

This article offers supplementary material which is provided at the end of the article.

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


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About the article

Received: 2018-05-01

Accepted: 2018-09-24

Published Online: 2018-10-26

Published in Print: 2018-11-27

Funding Source: National Science Foundation

Award identifier / Grant number: NSF-1456787

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.

Citation Information: Biological Chemistry, Volume 399, Issue 12, Pages 1375–1388, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2018-0240.

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