TY  - JOUR
A1  - Chatterjee, Deep
A1  - Preuss, Franziska Friederike
A1  - Dederer, Verena
A1  - Knapp, Stefan
A1  - Mathea, Sebastian
T1  - Structural aspects of LIMK regulation and pharmacology
T2  - Cells
N2  - 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.
KW  - LIMK1
KW  - LIMK2
KW  - kinase
KW  - phosphorylation
KW  - small-molecule inhibitor
KW  - catalytic mechanism
KW  - cofilin
KW  - actin cytoskeleton dynamics
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/81883
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-818834
SN  - 2073-4409
N1  - 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].
VL  - 11
IS  - 1, art. 142
SP  - 1
EP  - 12
PB  - MDPI
CY  - Basel
ER  -