4YBK

C-Helix-Out Dasatinib Analog Crystallized with c-Src Kinase

Summary for 4YBK

• Entry DOI: 10.2210/pdb4ybk/pdb
• Descriptor: Proto-oncogene tyrosine-protein kinase Src, 2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-N-(4-phenoxyphenyl)-1,3-thiazole-5-carboxamide (3 entities in total)
• Functional Keywords: protein kinase, c-helix-out, transferase
• Biological source: Gallus gallus (Chicken)
• Cellular location: Cell membrane : P00523
• Total number of polymer chains: 1
• Total formula weight: 33258.27

Authors

Kwarcinski, F.E.,Brandvold, K.B.,Johnson, T.K.,Phadke, S.,Meagher, J.L.,Seeliger, M.A.,Stuckey, J.A.,Soellner, M.B. (deposition date: 2015-02-18, release date: 2016-03-02, Last modification date: 2023-09-27)

Primary citation

Kwarcinski, F.E.,Brandvold, K.R.,Phadke, S.,Beleh, O.M.,Johnson, T.K.,Meagher, J.L.,Seeliger, M.A.,Stuckey, J.A.,Soellner, M.B.
Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.
Acs Chem.Biol., 11:1296-1304, 2016

PubMed Abstract: In the kinase field, there are many widely held tenets about conformation-selective inhibitors that have yet to be validated using controlled experiments. We have designed, synthesized, and characterized a series of kinase inhibitor analogues of dasatinib, an FDA-approved kinase inhibitor that binds the active conformation. This inhibitor series includes two Type II inhibitors that bind the DFG-out inactive conformation and two inhibitors that bind the αC-helix-out inactive conformation. Using this series of compounds, we analyze the impact that conformation-selective inhibitors have on target binding and kinome-wide selectivity.

PubMed: 26895387
DOI: 10.1021/acschembio.5b01018

Experimental method

X-RAY DIFFRACTION (2.5 Å)