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5x02

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'''Unreleased structure'''
 
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The entry 5x02 is ON HOLD until Paper Publication
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==Crystal structure of the FLT3 kinase domain bound to the inhibitor FF-10101==
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<StructureSection load='5x02' size='340' side='right' caption='[[5x02]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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Authors:
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5x02]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X02 FirstGlance]. <br>
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Description:
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F6M:N-[(2S)-1-[5-[2-[(4-cyanophenyl)amino]-4-(propylamino)pyrimidin-5-yl]pent-4-ynylamino]-1-oxidanylidene-propan-2-yl]-4-(dimethylamino)-N-methyl-but-2-enamide'>F6M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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[[Category: Unreleased Structures]]
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<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>
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<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=5x02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x02 OCA], [http://pdbe.org/5x02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x02 RCSB], [http://www.ebi.ac.uk/pdbsum/5x02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x02 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Defects in FLT3 are a cause of acute myelogenous leukemia (AML) [MIM:[http://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.<ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:14504097</ref> <ref>PMID:9737679</ref> <ref>PMID:18305215</ref> <ref>PMID:11290608</ref> <ref>PMID:8946930</ref> <ref>PMID:11442493</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.<ref>PMID:7507245</ref> <ref>PMID:10080542</ref> <ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:16627759</ref> <ref>PMID:18490735</ref> <ref>PMID:20111072</ref> <ref>PMID:21067588</ref> <ref>PMID:21262971</ref> <ref>PMID:21516120</ref> <ref>PMID:14504097</ref>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Fujikawa, N]]
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[[Category: Hagiwara, S]]
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[[Category: Hirano, D]]
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[[Category: Park, S Y]]
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[[Category: Sugiyama, K]]
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[[Category: Takasaki, M]]
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[[Category: Terada, D]]
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[[Category: Irreversible inhibitor complex]]
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[[Category: Kinase catalytic domain]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inihibitor complex]]
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[[Category: Tyrosine kinase]]

Revision as of 18:25, 24 January 2018

Crystal structure of the FLT3 kinase domain bound to the inhibitor FF-10101

5x02, resolution 2.40Å

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