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| {{STRUCTURE_2r4b| PDB=2r4b | SCENE= }} | | {{STRUCTURE_2r4b| PDB=2r4b | SCENE= }} |
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| '''ErbB4 kinase domain complexed with a thienopyrimidine inhibitor'''
| | ===ErbB4 kinase domain complexed with a thienopyrimidine inhibitor=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18287036}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18287036 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18287036}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transmembrane]] | | [[Category: Transmembrane]] |
| [[Category: Tyrosine-protein kinase]] | | [[Category: Tyrosine-protein kinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:13:17 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:10:30 2008'' |
