2r4b | pdb_00002r4b

ErbB4 kinase domain complexed with a thienopyrimidine inhibitor

spinqualitylabelsall models 2r4b, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2r4b is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GW7 Gene: ERBB4, HER4 (Homo sapiens) Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Analysis of the x-ray crystal structure of mono-substituted acetylenic thienopyrimidine 6 complexed with the ErbB family enzyme ErbB-4 revealed a covalent bond between the terminal carbon of the acetylene moiety and the sulfhydryl group of Cys-803 at the solvent interface. The identification of this covalent adduct suggested that acetylenic thienopyrimidine 6 and related analogs might also be capable of forming an analogous covalent adduct with EGFR, which has a conserved cysteine (797) near the ATP binding pocket. To test this hypothesis, we treated a truncated, catalytically competent form of EGFR (678-1020) with a structurally related propargylic amine (8). An investigation of the resulting complex by mass spectrometry revealed the formation of a covalent complex of thienopyrimidine 8 with Cys-797 of EGFR. This finding enabled us to readily assess the irreversibility of various inhibitors and also facilitated a structure-activity relationship understanding of the covalent modifying potential and biological activity of a series of acetylenic thienopyrimidine compounds with potent antitumor activity. Several ErbB family enzyme and cell potent 6-ethynyl thienopyrimidine kinase inhibitors were found to form covalent adducts with EGFR. 6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases.,Wood ER, Shewchuk LM, Ellis B, Brignola P, Brashear RL, Caferro TR, Dickerson SH, Dickson HD, Donaldson KH, Gaul M, Griffin RJ, Hassell AM, Keith B, Mullin R, Petrov KG, Reno MJ, Rusnak DW, Tadepalli SM, Ulrich JC, Wagner CD, Vanderwall DE, Waterson AG, Williams JD, White WL, Uehling DE Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2773-8. Epub 2008 Feb 19. PMID:18287036 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA