2XKC
Structure of Nek2 bound to aminopyrazine compound 14
Summary for 2XKC
| Entry DOI | 10.2210/pdb2xkc/pdb |
| Related | 2JAV 2W5A 2W5B 2W5H 2WQO 2XK3 2XK4 2XK6 2XK7 2XK8 2XKD 2XKE 2XKF 2XNM 2XNN 2XNO 2XNP |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-2-methylbenzoic acid, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | transferase, centrosome, mitosis |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Nucleus. Isoform 1: Nucleus, nucleolus. Isoform 2: Cytoplasm: P51955 |
| Total number of polymer chains | 1 |
| Total formula weight | 33199.70 |
| Authors | Mas-Droux, C.,Bayliss, R. (deposition date: 2010-07-07, release date: 2010-10-27, Last modification date: 2023-12-20) |
| Primary citation | Whelligan, D.K.,Solanki, S.,Taylor, D.,Thomson, D.W.,Cheung, K.M.,Boxall, K.,Mas-Droux, C.,Barillari, C.,Burns, S.,Grummitt, C.G.,Collins, I.,Van Montfort, R.L.,Aherne, G.W.,Bayliss, R.,Hoelder, S. Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization. J.Med.Chem., 53:7682-, 2010 Cited by PubMed Abstract: We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2. PubMed: 20936789DOI: 10.1021/JM1008727 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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