Structural aspects of LIMK regulation and pharmacology

  • Malfunction of the actin cytoskeleton is linked to numerous human diseases including neurological disorders and cancer. LIMK1 (LIM domain kinase 1) and its paralogue LIMK2 are two closely related kinases that control actin cytoskeleton dynamics. Consequently, they are potential therapeutic targets for the treatment of such diseases. In the present review, we describe the LIMK conformational space and its dependence on ligand binding. Furthermore, we explain the unique catalytic mechanism of the kinase, shedding light on substrate recognition and how LIMK activity is regulated. The structural features are evaluated for implications on the drug discovery process. Finally, potential future directions for targeting LIMKs pharmacologically, also beyond just inhibiting the kinase domain, are discussed.

Download full text files

Export metadata

Metadaten
Author:Deep ChatterjeeORCiDGND, Franziska Friederike PreussGND, Verena DedererGND, Stefan KnappORCiDGND, Sebastian MatheaORCiD
URN:urn:nbn:de:hebis:30:3-818834
DOI:https://doi.org/10.3390/cells11010142
ISSN:2073-4409
Parent Title (English):Cells
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2022/01/02
Date of first Publication:2022/01/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/02/14
Tag:LIMK1; LIMK2; actin cytoskeleton dynamics; catalytic mechanism; cofilin; kinase; phosphorylation; small-molecule inhibitor
Volume:11
Issue:1, art. 142
Article Number:142
Page Number:12
First Page:1
Last Page:12
Note:
The authors are grateful for support by the SGC, a registered charity (no. 1097737) that receives funds from AbbVie, BayerAG, Boehringer Ingelheim, the Canada Foundation for Innovation, Eshelman Institute for Innovation, Genentech, Genome Canada through Ontario Genomics Institute [OGI-196], EU/EFPIA/OICR/McGill/KTH/Diamond, Innovative Medicines Initiative 2 Joint Undertaking [EUbOPEN grant 875510].
Institutes:Biochemie, Chemie und Pharmazie
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International