7ojh: Difference between revisions

No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='7ojh' size='340' side='right'caption='[[7ojh]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='7ojh' size='340' side='right'caption='[[7ojh]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7ojh]] 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=7OJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJH FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJH 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=TTC:(S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3,4 6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE'>TTC</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]] 3.1&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7oj8|7oj8]]</div></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=TTC:(S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3,4 6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE'>TTC</scene></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='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=7ojh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ojh OCA], [https://pdbe.org/7ojh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ojh RCSB], [https://www.ebi.ac.uk/pdbsum/7ojh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ojh ProSAT]</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=7ojh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ojh OCA], [https://pdbe.org/7ojh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ojh RCSB], [https://www.ebi.ac.uk/pdbsum/7ojh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ojh ProSAT]</span></td></tr>
</table>
</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>
==See Also==
 
*[[ABC transporter 3D structures|ABC transporter 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ojh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: ABC-type xenobiotic transporter]]
[[Category: Human]]
[[Category: Large Structures]]
[[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]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA