1NVS
The Complex Structure Of Checkpoint Kinase Chk1/SB218078
Summary for 1NVS
| Entry DOI | 10.2210/pdb1nvs/pdb |
| Related | 1nvq |
| Descriptor | Serine/threonine-protein kinase Chk1, Peptide ASVSA, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | chk1-sb218078 complex, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: O14757 |
| Total number of polymer chains | 2 |
| Total formula weight | 33965.90 |
| Authors | Zhao, B.,Bower, M.J.,McDevitt, P.J.,Zhao, H.,Davis, S.T.,Johanson, K.O.,Green, S.M.,Concha, N.O.,Zhou, B.B. (deposition date: 2003-02-04, release date: 2003-04-08, Last modification date: 2023-08-16) |
| Primary citation | Zhao, B.,Bower, M.J.,McDevitt, P.J.,Zhao, H.,Davis, S.T.,Johanson, K.O.,Green, S.M.,Concha, N.O.,Zhou, B.B. Structural Basis for Chk1 Inhibition by UCN-01 J.Biol.Chem., 277:46609-46615, 2002 Cited by PubMed Abstract: Chk1 is a serine-threonine kinase that plays an important role in the DNA damage response, including G(2)/M cell cycle control. UCN-01 (7-hydroxystaurosporine), currently in clinical trials, has recently been shown to be a potent Chk1 inhibitor that abrogates the G(2)/M checkpoint induced by DNA-damaging agents. To understand the structural basis of Chk1 inhibition by UCN-01, we determined the crystal structure of the Chk1 kinase domain in complex with UCN-01. Chk1 structures with staurosporine and its analog SB-218078 were also determined. All three compounds bind in the ATP-binding pocket of Chk1, producing only slight changes in the protein conformation. Selectivity of UCN-01 toward Chk1 over cyclin-dependent kinases can be explained by the presence of a hydroxyl group in the lactam moiety interacting with the ATP-binding pocket. Hydrophobic interactions and hydrogen-bonding interactions were observed in the structures between UCN-01 and the Chk1 kinase domain. The high structural complementarity of these interactions is consistent with the potency and selectivity of UCN-01. PubMed: 12244092DOI: 10.1074/jbc.M201233200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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