2WQO

STRUCTURE OF NEK2 BOUND TO THE AMINOPYRIDINE CCT241950

Summary for 2WQO

• Entry DOI: 10.2210/pdb2wqo/pdb
• Related: 2JAV 2W5A 2W5B 2W5H 2WQM 2WQN
• Descriptor: SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[2-AMINO-5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL]BENZOIC ACID, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: kinase, nucleus, meiosis, mitosis, cytoplasm, alternative splicing, serine/threonine-protein kinase, metal-binding, phosphoprotein, nucleotide-binding, magnesium, cell cycle, atp-binding, transferase, coiled coil, polymorphism, cell division
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 33149.23

Authors

Mas-Droux, C.,Bayliss, R. (deposition date: 2009-08-24, release date: 2009-12-08, Last modification date: 2024-05-08)

Primary citation

Richards, M.W.,O'Regan, L.,Mas-Droux, C.,Blot, J.M.,Cheung, J.,Hoelder, S.,Fry, A.M.,Bayliss, R.
An Autoinhibitory Tyrosine Motif in the Cell-Cycle- Regulated Nek7 Kinase is Released Through Binding of Nek9.
Mol.Cell, 36:560-, 2009

PubMed Abstract: Mitosis is controlled by multiple protein kinases, many of which are abnormally expressed in human cancers. Nek2, Nek6, Nek7, and Nek9 are NIMA-related kinases essential for proper mitotic progression. We determined the atomic structure of Nek7 and discovered an autoinhibited conformation that suggests a regulatory mechanism not previously described in kinases. Additionally, Nek2 adopts the same conformation when bound to a drug-like molecule. In both structures, a tyrosine side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. Tyrosine mutants of Nek7 and the related kinase Nek6 are constitutively active. The activity of Nek6 and Nek7, but not the tyrosine mutant, is increased by interaction with the Nek9 noncatalytic C-terminal domain, suggesting a mechanism in which the tyrosine is released from its autoinhibitory position. The autoinhibitory conformation is common to three Neks and provides a potential target for selective kinase inhibitors.

PubMed: 19941817
DOI: 10.1016/J.MOLCEL.2009.09.038

Experimental method

X-RAY DIFFRACTION (2.167 Å)