Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
| Autor: | Chahrazade El Amri, Dirk Stratmann, Dalila Darmoul, Elodie Bosc, Michèle Reboud-Ravaux, Viktor Magdolen, Sabrina Aït Amiri, Feryel Soualmia |
|---|---|
| Přispěvatelé: | Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SOUALMIA, Feryel |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
small-organic modulators Proteases [SDV]Life Sciences [q-bio] Clinical Biochemistry Allosteric regulation serine protease allostery Molecular Dynamics Simulation Biochemistry Small Molecule Libraries Serine 03 medical and health sciences 0302 clinical medicine kallikrein-related peptidase 6 Allosteric Regulation Coumarins Humans Molecular Biology Molecular Structure Chemistry Mechanism (biology) KLK6 Kallikrein Small molecule [SDV] Life Sciences [q-bio] suicide substrate kallikrein-related peptidase 6 serine protease allostery small-organic modulators suicide substrate 030104 developmental biology 030220 oncology & carcinogenesis Kallikreins |
| Zdroj: | Biological Chemistry Biological Chemistry, 2018, 399, pp.1073-1078. ⟨10.1515/hsz-2017-0336⟩ |
| ISSN: | 1431-6730 1437-4315 |
| DOI: | 10.1515/hsz-2017-0336⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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