View source for 8wi3


==ND-hMRP5-inward open==
<StructureSection load='8wi3' size='340' side='right'caption='[[8wi3]], [[Resolution|resolution]] 3.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8wi3]] is a 1 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=8WI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WI3 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]] 3.38&#8491;</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=8wi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wi3 OCA], [https://pdbe.org/8wi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wi3 RCSB], [https://www.ebi.ac.uk/pdbsum/8wi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wi3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MRP5_HUMAN MRP5_HUMAN] ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (PubMed:10893247, PubMed:12637526, PubMed:12695538, PubMed:15899835, PubMed:17229149, PubMed:25964343). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (PubMed:12695538). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated (PubMed:10840050, PubMed:12435799, PubMed:12695538, PubMed:15899835). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity).[UniProtKB:Q9R1X5]<ref>PMID:10840050</ref> <ref>PMID:10893247</ref> <ref>PMID:12435799</ref> <ref>PMID:12637526</ref> <ref>PMID:12695538</ref> <ref>PMID:15899835</ref> <ref>PMID:17229149</ref> <ref>PMID:24836561</ref> <ref>PMID:25964343</ref> <ref>PMID:26515061</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.

Inhibition and transport mechanisms of the ABC transporter hMRP5.,Huang Y, Xue C, Bu R, Wu C, Li J, Zhang J, Chen J, Shi Z, Chen Y, Wang Y, Liu Z Nat Commun. 2024 Jun 6;15(1):4811. doi: 10.1038/s41467-024-49204-1. PMID:38844452<ref>PMID:38844452</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8wi3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Huang Y]]
[[Category: Liu ZM]]