2r4b
From Proteopedia
(New page: 200px {{Structure |PDB= 2r4b |SIZE=350|CAPTION= <scene name='initialview01'>2r4b</scene>, resolution 2.40Å |SITE= <scene name='pdbsite=AC1:Gw7+Binding+Site+...) |
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|PDB= 2r4b |SIZE=350|CAPTION= <scene name='initialview01'>2r4b</scene>, resolution 2.40Å | |PDB= 2r4b |SIZE=350|CAPTION= <scene name='initialview01'>2r4b</scene>, resolution 2.40Å | ||
|SITE= <scene name='pdbsite=AC1:Gw7+Binding+Site+For+Residue+A+1'>AC1</scene> and <scene name='pdbsite=AC2:Gw7+Binding+Site+For+Residue+B+1'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:Gw7+Binding+Site+For+Residue+A+1'>AC1</scene> and <scene name='pdbsite=AC2:Gw7+Binding+Site+For+Residue+B+1'>AC2</scene> | ||
| - | |LIGAND= <scene name='pdbligand=GW7:'>GW7</scene> | + | |LIGAND= <scene name='pdbligand=GW7:N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-ETHYLTHIENO[3,2-D]PYRIMIDIN-4-AMINE'>GW7</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span> |
|GENE= ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r4b OCA], [http://www.ebi.ac.uk/pdbsum/2r4b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2r4b RCSB]</span> | ||
}} | }} | ||
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[[Category: Shewchuk, L M.]] | [[Category: Shewchuk, L M.]] | ||
[[Category: Uehling, D E.]] | [[Category: Uehling, D E.]] | ||
| - | [[Category: GW7]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:56:27 2008'' |
Revision as of 01:56, 31 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | ERBB4, HER4 (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ErbB4 kinase domain complexed with a thienopyrimidine inhibitor
Overview
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.
About this Structure
2R4B is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 04:56:27 2008
