3bbt
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:Fmm+Binding+Site+For+Residue+B+91'>AC1</scene> and <scene name='pdbsite=AC2:Fmm+Binding+Site+For+Residue+D+91'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:Fmm+Binding+Site+For+Residue+B+91'>AC1</scene> and <scene name='pdbsite=AC2:Fmm+Binding+Site+For+Residue+D+91'>AC2</scene> | ||
|LIGAND= <scene name='pdbligand=FMM:N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE'>FMM</scene> | |LIGAND= <scene name='pdbligand=FMM:N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE'>FMM</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=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=smart00220 S_TKc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd05110 PTKc_HER4]</span> | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bbt OCA], [http://www.ebi.ac.uk/pdbsum/3bbt PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=3bbt RCSB]</span> | ||
}} | }} | ||
'''crystal structure of the ErbB4 kinase in complex with lapatinib''' | '''crystal structure of the ErbB4 kinase in complex with lapatinib''' | ||
| + | |||
| + | ==Overview== | ||
| + | HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members. | ||
==About this Structure== | ==About this Structure== | ||
3BBT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BBT OCA]. | 3BBT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BBT OCA]. | ||
| + | |||
| + | ==Reference== | ||
| + | Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase., Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ, Structure. 2008 Mar;16(3):460-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18334220 18334220] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Qiu, C.]] | [[Category: Qiu, C.]] | ||
| - | [[Category: FMM]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
| Line 31: | Line 38: | ||
[[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 Wed Mar 26 10:03:22 2008'' |
Revision as of 08:03, 26 March 2008
| |||||||
| , resolution 2.800Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | ERBB4, HER4 (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Domains: | S_TKc, PTKc_HER4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
crystal structure of the ErbB4 kinase in complex with lapatinib
Overview
HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members.
About this Structure
3BBT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase., Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ, Structure. 2008 Mar;16(3):460-7. PMID:18334220
Page seeded by OCA on Wed Mar 26 10:03:22 2008
