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Updated: Feb 12, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
Feryel Soualmia1, Elodie Bosc1, Sabrina Aït Amiri1
1Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France.
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.
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