2jav | pdb_00002jav

HUMAN KINASE WITH PYRROLE-INDOLINONE LIGAND

spinqualitylabelsall models 2jav, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jav is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 2cl1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5Z5 Related: 2cl1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [NEK2_HUMAN] Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The dimeric Ser/Thr kinase Nek2 regulates centrosome cohesion and separation through phosphorylation of structural components of the centrosome, and aberrant regulation of Nek2 activity can lead to aneuploid defects characteristic of cancer cells. Mutational analysis of autophosphorylation sites within the kinase domain identified by mass spectrometry shows a complex pattern of positive and negative regulatory effects on kinase activity that are correlated with effects on centrosomal splitting efficiency in vivo. The 2.2-A resolution x-ray structure of the Nek2 kinase domain in complex with a pyrrole-indolinone inhibitor reveals an inhibitory helical motif within the activation loop. This helix presents a steric barrier to formation of the active enzyme and generates a surface that may be exploitable in the design of specific inhibitors that selectively target the inactive state. Comparison of this "auto-inhibitory" conformation with similar arrangements in cyclin-dependent kinase 2 and epidermal growth factor receptor kinase suggests a role for dimerization-dependent allosteric regulation that combines with autophosphorylation and protein phosphatase 1c phosphatase activity to generate the precise spatial and temporal control required for Nek2 function in centrosomal maturation. Structure and regulation of the human Nek2 centrosomal kinase.,Rellos P, Ivins FJ, Baxter JE, Pike A, Nott TJ, Parkinson DM, Das S, Howell S, Fedorov O, Shen QY, Fry AM, Knapp S, Smerdon SJ J Biol Chem. 2007 Mar 2;282(9):6833-42. Epub 2006 Dec 31. PMID:17197699 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase

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