6vxj
From Proteopedia
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==Structure of ABCG2 bound to SN38== | ==Structure of ABCG2 bound to SN38== | ||
| - | <StructureSection load='6vxj' size='340' side='right'caption='[[6vxj]]' scene=''> | + | <StructureSection load='6vxj' size='340' side='right'caption='[[6vxj]], [[Resolution|resolution]] 4.10Å' 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=6VXJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VXJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vxj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VXJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VXJ 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=6vxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxj OCA], [http://pdbe.org/6vxj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vxj RCSB], [http://www.ebi.ac.uk/pdbsum/6vxj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxj 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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=RS4:7-ethyl-10-hydroxycamptothecin'>RS4</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ABC-type_xenobiotic_transporter ABC-type xenobiotic transporter], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.6.2.2 7.6.2.2] </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=6vxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxj OCA], [http://pdbe.org/6vxj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vxj RCSB], [http://www.ebi.ac.uk/pdbsum/6vxj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ABCG2_HUMAN ABCG2_HUMAN]] High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin.<ref>PMID:12958161</ref> <ref>PMID:20705604</ref> <ref>PMID:22132962</ref> <ref>PMID:23189181</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ABCG2 is an ABC transporter that extrudes a variety of compounds from cells, and presents an obstacle in treating chemotherapy-resistant cancers. Despite recent structural insights, no anticancer drug bound to ABCG2 has been resolved, and the mechanisms of multidrug transport remain obscure. Such a gap of knowledge limits the development of novel compounds that block or evade this critical molecular pump. Here we present single-particle cryo-EM studies of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics. Without the binding of conformation-selective antibody fragments or inhibitors, the resting ABCG2 adopts a closed conformation. Our cryo-EM, biochemical, and functional analyses reveal the binding mode of three chemotherapeutic compounds, demonstrate how these molecules open the closed conformation of the transporter, and establish that imatinib is particularly effective in stabilizing the inward facing conformation of ABCG2. Together these studies reveal the previously unrecognized conformational cycle of ABCG2. | ||
| + | |||
| + | ABCG2 transports anticancer drugs via a closed-to-open switch.,Orlando BJ, Liao M Nat Commun. 2020 May 8;11(1):2264. doi: 10.1038/s41467-020-16155-2. PMID:32385283<ref>PMID:32385283</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vxj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: ABC-type xenobiotic transporter]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Liao M]] | + | [[Category: Liao, M]] |
| - | [[Category: Orlando | + | [[Category: Orlando, B J]] |
| + | [[Category: Abc transporter]] | ||
| + | [[Category: Abcg2]] | ||
| + | [[Category: Nanodisc]] | ||
| + | [[Category: Sn38]] | ||
| + | [[Category: Translocase]] | ||
Revision as of 06:13, 20 May 2020
Structure of ABCG2 bound to SN38
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