2XNO

Structure of Nek2 bound to CCT243779

Summary for 2XNO

• Entry DOI: 10.2210/pdb2xno/pdb
• Related: 2JAV 2W5A 2W5B 2W5H 2WQO 2XK3 2XK4 2XK6 2XK7 2XK8 2XKC 2XKD 2XKE 2XKF 2XNM 2XNN 2XNP
• Descriptor: SERINE/THREONINE-PROTEIN KINASE NEK2, 5-{6-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-1-yl}-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: transferase, centrosome, mitosis, cell cycle
• 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: 34116.92

Authors

Mas-Droux, C.,Bayliss, R. (deposition date: 2010-08-05, release date: 2011-03-30, Last modification date: 2023-12-20)

Primary citation

Solanki, S.,Innocenti, P.,Mas-Droux, C.,Boxall, K.,Barillari, C.,Van Montfort, R.L.,Aherne, G.W.,Bayliss, R.,Hoelder, S.
Benzimidazole Inhibitors Induce a Dfg-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure-Activity Relationship.
J.Med.Chem., 54:1626-, 2011

PubMed Abstract: We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

PubMed: 21366329
DOI: 10.1021/JM1011726

Experimental method

X-RAY DIFFRACTION (1.98 Å)