2qlq
From Proteopedia
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|PDB= 2qlq |SIZE=350|CAPTION= <scene name='initialview01'>2qlq</scene>, resolution 2.33Å | |PDB= 2qlq |SIZE=350|CAPTION= <scene name='initialview01'>2qlq</scene>, resolution 2.33Å | ||
|SITE= <scene name='pdbsite=AC1:Sr2+Binding+Site+For+Residue+A+1345'>AC1</scene>, <scene name='pdbsite=AC2:Sr2+Binding+Site+For+Residue+A+1483'>AC2</scene> and <scene name='pdbsite=AC3:Sr2+Binding+Site+For+Residue+B+1345'>AC3</scene> | |SITE= <scene name='pdbsite=AC1:Sr2+Binding+Site+For+Residue+A+1345'>AC1</scene>, <scene name='pdbsite=AC2:Sr2+Binding+Site+For+Residue+A+1483'>AC2</scene> and <scene name='pdbsite=AC3:Sr2+Binding+Site+For+Residue+B+1345'>AC3</scene> | ||
| - | |LIGAND= <scene name='pdbligand=SR2:'>SR2</scene> | + | |LIGAND= <scene name='pdbligand=SR2:(2E)-N-{4-[(3-BROMOPHENYL)AMINO]QUINAZOLIN-6-YL}-4-(DIMETHYLAMINO)BUT-2-ENAMIDE'>SR2</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span> |
|GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]) | |GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2qi8|2QI8]], [[2qig|2QIG]], [[2hwp|2HWP]], [[2qq7|2QQ7]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qlq OCA], [http://www.ebi.ac.uk/pdbsum/2qlq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qlq RCSB]</span> | ||
}} | }} | ||
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[[Category: Rauh, D.]] | [[Category: Rauh, D.]] | ||
[[Category: Rode, H B.]] | [[Category: Rode, H B.]] | ||
| - | [[Category: SR2]] | ||
[[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 04:50:39 2008'' |
Revision as of 01:50, 31 March 2008
| |||||||
| , resolution 2.33Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | |||||||
| Gene: | SRC (Gallus gallus) | ||||||
| Activity: | Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 | ||||||
| Related: | 2QI8, 2QIG, 2HWP, 2QQ7
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of src kinase with covalent inhibitor XXX
Overview
Resistance to kinase- targeted cancer drugs has recently been linked to a single point mutation in the ATP binding site of the kinase. In EGFR, the crucial Thr790 gatekeeper residue is mutated to a Met and prevents reversible ATP competitive inhibitors from binding. Irreversible 4-(phenylamino)quinazolines have been shown to overcome this drug resistance and are currently in clinical trials. In order to obtain a detailed structural understanding of how irreversible inhibitors overcome drug resistance, we used Src kinase as a model system for drug resistant EGFR-T790M. We report the first crystal structure of a drug resistant kinase in complex with an irreversible inhibitor. This 4-(phenylamino)quinazoline inhibits wild type and drug resistant EGFR in vitro at low nM concentrations. The co-crystal structure of drug resistant cSrc-T338M kinase domain provides the structural basis of this activity.
About this Structure
2QLQ is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
Reference
Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR., Michalczyk A, Kluter S, Rode HB, Simard JR, Grutter C, Rabiller M, Rauh D, Bioorg Med Chem. 2008 Feb 20;. PMID:18316192
Page seeded by OCA on Mon Mar 31 04:50:39 2008
Categories: Gallus gallus | Non-specific protein-tyrosine kinase | Single protein | Gruetter, C. | Michalczyk, A. | Rauh, D. | Rode, H B. | Alternative splicing | Atp-binding | Drug resistance | Irreversible inhibitor | Kovalent inhibitor | Lipoprotein | Myristate | Nucleotide-binding | Phosphorylation | Proto-oncogene | Sh2 domain | Sh3 domain | Src kinase domain | Transferase | Tyrosine-protein kinase
