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Structural Aspects of LIMK Regulation and Pharmacology.

ABSTRACT: 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.

SUBMITTER: Chatterjee D

PROVIDER: S-EPMC8750758 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Structural Aspects of LIMK Regulation and Pharmacology.

Chatterjee Deep D Preuss Franziska F Dederer Verena V Knapp Stefan S Mathea Sebastian S

Cells 20220102 1

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 ...[more]

PMID: 35011704

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Dataset Information

Structural Aspects of LIMK Regulation and Pharmacology.

Publications

Structural Aspects of LIMK Regulation and Pharmacology.

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