7oj8: Difference between revisions

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 <StructureSection load='7oj8' size='340' side='right'caption='[[7oj8]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7oj8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJ8 FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJ8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FY5:estrone+3-sulfate'>FY5</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABCG2, ABCP, BCRP, BCRP1, MXR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FY5:estrone+3-sulfate'>FY5</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/ABC-type_xenobiotic_transporter ABC-type xenobiotic transporter], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7oj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oj8 OCA], [https://pdbe.org/7oj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oj8 RCSB], [https://www.ebi.ac.uk/pdbsum/7oj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oj8 ProSAT]</span></td></tr>
 </table>
-== Function ==
-[[https://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 a multidrug transporter that affects drug pharmacokinetics and contributes to multidrug resistance of cancer cells. In previously reported structures, the reaction cycle was halted by the absence of substrates or ATP, mutation of catalytic residues, or the presence of small-molecule inhibitors or inhibitory antibodies. Here we present cryo-EM structures of ABCG2 under turnover conditions containing either the endogenous substrate estrone-3-sulfate or the exogenous substrate topotecan. We find two distinct conformational states in which both the transport substrates and ATP are bound. Whereas the state turnover-1 features more widely separated NBDs and an accessible substrate cavity between the TMDs, turnover-2 features semi-closed NBDs and an almost fully occluded substrate cavity. Substrate size appears to control which turnover state is mainly populated. The conformational changes between turnover-1 and turnover-2 states reveal how ATP binding is linked to the closing of the cytoplasmic side of the TMDs. The transition from turnover-1 to turnover-2 is the likely bottleneck or rate-limiting step of the reaction cycle, where the discrimination of substrates and inhibitors occurs.
-Structures of ABCG2 under turnover conditions reveal a key step in the drug transport mechanism.,Yu Q, Ni D, Kowal J, Manolaridis I, Jackson SM, Stahlberg H, Locher KP Nat Commun. 2021 Jul 19;12(1):4376. doi: 10.1038/s41467-021-24651-2. PMID:34282134<ref>PMID:34282134</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7oj8" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: ABC-type xenobiotic transporter]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Jackson, S M]]
+[[Category: Jackson SM]]
-[[Category: Kowal, J]]
+[[Category: Kowal J]]
-[[Category: Locher, K P]]
+[[Category: Locher KP]]
-[[Category: Manolaridis, I]]
+[[Category: Manolaridis I]]
-[[Category: Ni, D]]
+[[Category: Ni D]]
-[[Category: Stahlberg, H]]
+[[Category: Stahlberg H]]
-[[Category: Yu, Q]]
+[[Category: Yu Q]]
-[[Category: Abc transporter plasma membrane atp multidrug resistance]]
-[[Category: Transport protein]]