PDBsum entry 4yc8

Transferase

PDB id: 4yc8

Contents

Protein chains

259 a.a.

Ligands

4B7 ×2

EDO ×2

MES ×2

Waters ×11

PDB id:

4yc8

Name:

Transferase

Title:

C-helix-out binding of dasatinib analog to c-abl kinase

Structure:

Tyrosine-protein kinase abl1. Chain: a, b. Fragment: unp residues 248-531. Synonym: abelson murine leukemia viral oncogene homolog 1,abelson tyrosine-protein kinase 1,proto-oncogenE C-abl,p150. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abl1, abl, jtk7. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.90Å R-factor: 0.199 R-free: 0.240

Authors:

F.E.Kwarcinski,K.B.Brandvold,T.J.Johnson,S.Phadke,J.L.Meagher, M.A.Seeliger,J.A.Stuckey,M.B.Soellner

Key ref:

F.E.Kwarcinski et al. (2016). Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity. Acs Chem Biol, 11, 1296-1304. PubMed id: 26895387 DOI: 10.1021/acschembio.5b01018

Date:

19-Feb-15 Release date: 02-Mar-16

Protein chains

P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1 from Homo sapiens

Seq: 1130 a.a.

Struc: 259 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/acschembio.5b01018

Acs Chem Biol 11:1296-1304 (2016)

PubMed id: 26895387

Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.

F.E.Kwarcinski, K.R.Brandvold, S.Phadke, O.M.Beleh, T.K.Johnson, J.L.Meagher, M.A.Seeliger, J.A.Stuckey, M.B.Soellner.

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.