crystal structure analysisinter-lobe arrangementmultiscale enhanced samplingProtein kinases play important roles in cellular signaling and have been one of the best studied drug targets. The kinase domain of epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that has been extensively ...
Epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small cell lung cancers (NSCLCs), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the anti-EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib initially...
图 1 EGFR 酪氨酸激酶区域晶体结构 A活化状态酪氨酸激酶功能结构域;B小分子 TKI 吉非替尼结合于 TK 区的晶体结构;C小分子 TKI 拉帕替尼结合于 TK 区的晶体结构 Fig 1 EGFR tyrosine kinase (TK) crystal structures Aillustration of the active-state locations of the major structural ...
2.4I24 Structure of T790MEGFR kinase domain co-crystallized with dacomitinib. Insights into the Aberrant Activity of Mutant EGFR Kinase Domain and Drug Recognition. (2013) Structure 21: 209-219 3.4HJOCrystalstructure of the inactive EGFR tyrosine kinase domain with erlotinib. Erlotinib binds both ina...
By contrast, the T790M mutation confers a higher SCIENTIFIC REPORTS | 4 : 5868 | DOI: 10.1038/srep05868 1 www.nature.com/scientificreports Figure 1 | Schematic representation (ribbon shape) of crystal structure of EGFR kinase domain bound to gefitinib by PyMol. Stick representation of gefitinib...
However, most EGFR mutations focus on the kinase domain.36 Thus, inducing EGFR degradation by targeting the kinase region may not avoid EGFR mutations. An alternative approach to EGFR degradation is to target the ECD. It has been reported recently that T315 initiates EGFR degradation by binding ...
Although all ERBB/HER receptors share similar domain architecture, ERBB2/HER2 binds with no known ligand and ERBB3/HER3 harbors a barely active kinase domain. Like other RTKs, ERBB/HER proteins signal downstream through the ERK/MAPK and PI3K/AKT pathways. However, ERBB/HER proteins are ...
(TKIs).1,2A study of the crystal structure and kinetics of EGFR exon 20 insertion mutations highlights a pattern of activation in the EGFR kinase domain not associated with substantial structural or kinetic changes so a...
The crystal structure of EGFR kinase domain (L858R, T790M, V948R) in complex with the covalent inhibitor CO-1686 is under ID 5UWD in the PDB. Author Contributions S.N., M.M.D., and B.F.C. designed the experiments; S.N. and M.M.D. performed the experiments and analyzed data; ...
EGFR kinase pocket to affect receptor function, we performed a combination of molecular docking, MD and ANM analyses. The wild type EGFR crystal structure in complex with erlotinib (PDB 1M17) was used as the basis for the analyses. A Mg2+ion was placed between D855, N842 and a water ...