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==Structure of Human ROS1 Kinase Domain in Complex with Crizotinib==
==Structure of Human ROS1 Kinase Domain in Complex with Crizotinib==
<StructureSection load='3zbf' size='340' side='right' caption='[[3zbf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='3zbf' size='340' side='right'caption='[[3zbf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3zbf]] is a 1 chain structure with 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=3ZBF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZBF FirstGlance]. <br>
<table><tr><td colspan='2'>[[3zbf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZBF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=VGH:3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(1-PIPERIDIN-4-YL-1H-PYRAZOL-4-YL)PYRIDIN-2-AMINE'>VGH</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VGH:3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(1-PIPERIDIN-4-YL-1H-PYRAZOL-4-YL)PYRIDIN-2-AMINE'>VGH</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zbf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zbf RCSB], [http://www.ebi.ac.uk/pdbsum/3zbf PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zbf OCA], [https://pdbe.org/3zbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zbf RCSB], [https://www.ebi.ac.uk/pdbsum/3zbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zbf ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/ROS1_HUMAN ROS1_HUMAN]] Note=A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells.<ref>PMID:12661006</ref>
[https://www.uniprot.org/uniprot/ROS1_HUMAN ROS1_HUMAN] Note=A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells.<ref>PMID:12661006</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ROS1_HUMAN ROS1_HUMAN]] Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.<ref>PMID:11094073</ref> <ref>PMID:16885344</ref>
[https://www.uniprot.org/uniprot/ROS1_HUMAN ROS1_HUMAN] Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.<ref>PMID:11094073</ref> <ref>PMID:16885344</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 3zbf" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Tyrosine kinase|Tyrosine kinase]]
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Large Structures]]
[[Category: Brooun, A]]
[[Category: Brooun A]]
[[Category: Deng, Y]]
[[Category: Deng Y]]
[[Category: Liu, W]]
[[Category: Liu W]]
[[Category: McTigue, M]]
[[Category: McTigue M]]
[[Category: Stewart, A]]
[[Category: Stewart A]]
[[Category: Transferase]]
[[Category: Tyrosine kinase]]