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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 399, Issue 9

Issues

Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism

Feryel Soualmia
  • Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France
  • Other articles by this author:
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/ Elodie Bosc
  • Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France
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/ Sabrina Aït Amiri
  • Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France
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/ Dirk Stratmann
  • Sorbonne University, Faculty of Sciences and Engineering, IMPMC, UMR 7590 CNRS-UPMC-MNHN-IRD, F-75252 Paris, France
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/ Viktor Magdolen
  • Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University Munich, D-81675 Munich, Germany
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/ Dalila Darmoul
  • Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Louis, F-75010 Paris, France
  • Université Paris Diderot, Sorbonne Paris Cité, UMRS- S976, F-75010 Paris, France
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/ Michèle Reboud-Ravaux
  • Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France
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/ Chahrazade El Amri
  • Corresponding author
  • Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France
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Published Online: 2018-04-11 | DOI: https://doi.org/10.1515/hsz-2017-0336

Abstract

The activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered as an attractive therapeutical target. In this short report, we depict some novel findings on the regulation of the KLK6 activity. Namely, we identified mechanism-based inhibitors (suicide substrates) from an in-house library of 6-substituted coumarin-3-carboxylate derivatives. In addition, a molecular dynamics study evidenced the allosteric behavior of KLK6 similar to that previously observed for some trypsin-like serine proteases. This allosteric behavior together with the coumarinic scaffold bring new opportunities for the design of KLK6 potent activity modulators, useful as therapeutics or activity-based probes.

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

Keywords: kallikrein-related peptidase 6; serine protease allostery; small-organic modulators; suicide substrate

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About the article

Received: 2017-12-28

Accepted: 2018-03-26

Published Online: 2018-04-11

Published in Print: 2018-09-25


Citation Information: Biological Chemistry, Volume 399, Issue 9, Pages 1073–1078, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2017-0336.

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