8phw: Difference between revisions

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-'''Unreleased structure'''
-The entry 8phw is ON HOLD  until Paper Publication
+==Human OATP1B1==
+<StructureSection load='8phw' size='340' side='right'caption='[[8phw]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8phw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PHW FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FY5:estrone+3-sulfate'>FY5</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></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=8phw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8phw OCA], [https://pdbe.org/8phw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8phw RCSB], [https://www.ebi.ac.uk/pdbsum/8phw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8phw ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SO1B1_HUMAN SO1B1_HUMAN] Prediction of statin toxicity;Rotor syndrome. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/SO1B1_HUMAN SO1B1_HUMAN] Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:12196548, PubMed:11159893, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15970799, PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16627748, PubMed:16624871). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463).<ref>PMID:10358072</ref> <ref>PMID:10601278</ref> <ref>PMID:10873595</ref> <ref>PMID:11159893</ref> <ref>PMID:12196548</ref> <ref>PMID:12568656</ref> <ref>PMID:15159445</ref> <ref>PMID:15970799</ref> <ref>PMID:16624871</ref> <ref>PMID:16627748</ref> <ref>PMID:17412826</ref> <ref>PMID:19129463</ref> <ref>PMID:22232210</ref> <ref>PMID:23243220</ref> <ref>PMID:26383540</ref> <ref>PMID:26979622</ref> <ref>PMID:35307651</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.
-Authors:
+Structure of human drug transporters OATP1B1 and OATP1B3.,Ciuta AD, Nosol K, Kowal J, Mukherjee S, Ramirez AS, Stieger B, Kossiakoff AA, Locher KP Nat Commun. 2023 Sep 18;14(1):5774. doi: 10.1038/s41467-023-41552-8. PMID:37723174<ref>PMID:37723174</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8phw" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ciuta A-D]]
+[[Category: Kossiakoff AA]]
+[[Category: Kowal J]]
+[[Category: Locher KP]]
+[[Category: Mukherjee S]]
+[[Category: Nosol K]]
+[[Category: Ramirez AS]]
+[[Category: Stieger B]]