2gs7
From Proteopedia
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|PDB= 2gs7 |SIZE=350|CAPTION= <scene name='initialview01'>2gs7</scene>, resolution 2.600Å | |PDB= 2gs7 |SIZE=350|CAPTION= <scene name='initialview01'>2gs7</scene>, resolution 2.600Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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= EGFR, ERBB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= EGFR, ERBB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2gs2|2GS2]], [[2gs6|2GS6]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gs7 OCA], [http://www.ebi.ac.uk/pdbsum/2gs7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gs7 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization. | The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]], Nonsmall cell lung cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Shen, K.]] | [[Category: Shen, K.]] | ||
[[Category: Zhang, X.]] | [[Category: Zhang, X.]] | ||
| - | [[Category: ANP]] | ||
| - | [[Category: IOD]] | ||
| - | [[Category: MG]] | ||
[[Category: amp-pnp]] | [[Category: amp-pnp]] | ||
[[Category: egfr]] | [[Category: egfr]] | ||
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[[Category: kinase]] | [[Category: 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 03:20:46 2008'' |
Revision as of 00:20, 31 March 2008
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| , resolution 2.600Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | EGFR, ERBB1 (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 2GS2, 2GS6
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP
Overview
The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization.
About this Structure
2GS7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor., Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J, Cell. 2006 Jun 16;125(6):1137-49. PMID:16777603
Page seeded by OCA on Mon Mar 31 03:20:46 2008
