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Crystal structure of human RIOK2 bound to a specific inhibitor.

ABSTRACT: The RIO kinases (RIOKs) are a universal family of atypical kinases that are essential for assembly of the pre-40S ribosome complex. Here, we present the crystal structure of human RIO kinase 2 (RIOK2) bound to a specific inhibitor. This first crystal structure of an inhibitor-bound RIO kinase reveals the binding mode of the inhibitor and explains the structure-activity relationship of the inhibitor series. The inhibitor binds in the ATP-binding site and forms extensive hydrophobic interactions with residues at the entrance to the ATP-binding site. Analysis of the conservation of active site residues reveals the reasons for the specificity of the inhibitor for RIOK2 over RIOK1 and RIOK3, and it provides a template for inhibitor design against the human RIOK family.

SUBMITTER: Wang J

PROVIDER: S-EPMC6501643 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Crystal structure of human RIOK2 bound to a specific inhibitor.

Wang Jing J Varin Thibault T Vieth Michal M Elkins Jonathan M JM

Open biology 20190401 4

The RIO kinases (RIOKs) are a universal family of atypical kinases that are essential for assembly of the pre-40S ribosome complex. Here, we present the crystal structure of human RIO kinase 2 (RIOK2) bound to a specific inhibitor. This first crystal structure of an inhibitor-bound RIO kinase reveals the binding mode of the inhibitor and explains the structure-activity relationship of the inhibitor series. The inhibitor binds in the ATP-binding site and forms extensive hydrophobic interactions w ...[more]

PMID: 30991936

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