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==Crystal structure of MerTK kinase domain in complex with Gilteritinib== | ==Crystal structure of MerTK kinase domain in complex with Gilteritinib== | ||
<StructureSection load='7ab1' size='340' side='right'caption='[[7ab1]]' scene=''> | <StructureSection load='7ab1' size='340' side='right'caption='[[7ab1]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AB1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AB1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ab1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AB1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AB1 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7ab1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ab1 OCA], [http://pdbe.org/7ab1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ab1 RCSB], [http://www.ebi.ac.uk/pdbsum/7ab1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ab1 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C6F:6-ethyl-3-[[3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]amino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide'>C6F</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[7aax|7aax]], [[7aay|7aay]], [[7aaz|7aaz]], [[7ab0|7ab0]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MERTK, MER ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7ab1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ab1 OCA], [http://pdbe.org/7ab1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ab1 RCSB], [http://www.ebi.ac.uk/pdbsum/7ab1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ab1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[http://omim.org/entry/613862 613862]]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: McCoull W]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Nissink | [[Category: McCoull, W]] | ||
[[Category: Overman | [[Category: Nissink, J W.M]] | ||
[[Category: Pflug A]] | [[Category: Overman, R C]] | ||
[[Category: Rawlins | [[Category: Pflug, A]] | ||
[[Category: Schimpl M]] | [[Category: Rawlins, P B]] | ||
[[Category: Truman C]] | [[Category: Schimpl, M]] | ||
[[Category: Underwood E]] | [[Category: Truman, C]] | ||
[[Category: Warwicker J]] | [[Category: Underwood, E]] | ||
[[Category: Winter-Holt J]] | [[Category: Warwicker, J]] | ||
[[Category: Winter-Holt, J]] | |||
[[Category: Structure-based drug design]] | |||
[[Category: Transferase]] | |||
[[Category: Type 1 inhibitor]] | |||
[[Category: Tyrosine kinase inhibitor]] | |||
Revision as of 10:40, 4 November 2020
Crystal structure of MerTK kinase domain in complex with GilteritinibCrystal structure of MerTK kinase domain in complex with Gilteritinib
Structural highlights
Disease[MERTK_HUMAN] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:613862]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.[1] Function[MERTK_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.[2] References
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