3TKI

Crystal structure of Chk1 in complex with inhibitor S25

Summary for 3TKI

• Entry DOI: 10.2210/pdb3tki/pdb
• Related: 3TKH
• Descriptor: Serine/threonine-protein kinase Chk1, SULFATE ION, N-(2-aminoethyl)-5-(2-{[4-(morpholin-4-yl)pyridin-2-yl]amino}-1,3-thiazol-5-yl)pyridine-3-carboxamide, ... (4 entities in total)
• Functional Keywords: chk1, kinase, cell checkpoint, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 37443.72

Authors

Yan, Y.,Ikuta, M. (deposition date: 2011-08-26, release date: 2012-04-11, Last modification date: 2023-09-13)

Primary citation

Dudkin, V.Y.,Rickert, K.,Kreatsoulas, C.,Wang, C.,Arrington, K.L.,Fraley, M.E.,Hartman, G.D.,Yan, Y.,Ikuta, M.,Stirdivant, S.M.,Drakas, R.A.,Walsh, E.S.,Hamilton, K.,Buser, C.A.,Lobell, R.B.,Sepp-Lorenzino, L.
Pyridyl aminothiazoles as potent inhibitors of Chk1 with slow dissociation rates.
Bioorg.Med.Chem.Lett., 22:2609-2612, 2012

PubMed Abstract: Pyridyl aminothiazoles comprise a novel class of ATP-competitive Chk1 inhibitors with excellent inhibitory potential. Modification of the core with ethylenediamine amides provides compounds with low picomolar potency and very high residence times. Investigation of binding parameters of such compounds using X-ray crystallography and molecular dynamics simulations revealed multiple hydrogen bonds to the enzyme backbone as well as stabilization of the conserved water molecules network in the hydrophobic binding region.

PubMed: 22374217
DOI: 10.1016/j.bmcl.2012.01.110

Experimental method

X-RAY DIFFRACTION (1.6 Å)