View source for 5mra


==human SCBD (sorcin calcium binding domain) in complex with doxorubicin==
<StructureSection load='5mra' size='340' side='right'caption='[[5mra]], [[Resolution|resolution]] 3.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mra]] is a 4 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=5MRA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.74&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DM2:DOXORUBICIN'>DM2</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5mra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mra OCA], [https://pdbe.org/5mra PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mra RCSB], [https://www.ebi.ac.uk/pdbsum/5mra PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mra ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SORCN_HUMAN SORCN_HUMAN] Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels.<ref>PMID:17699613</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sorcin is a calcium binding protein that plays an important role in multidrug resistance (MDR) in tumors, since its expression confers resistance to doxorubicin and to other chemotherapeutic drugs. In this study, we show that Sorcin is able to bind doxorubicin, vincristine, paclitaxel and cisplatin directly and with high affinity. The high affinity binding of doxorubicin to sorcin has been demonstrated with different techniques, that is, surface plasmon resonance, fluorescence titration and X-ray diffraction. Although the X-ray structure of sorcin in complex with doxorubicin has been solved at low resolution, it allows the identification of one of the two doxorubicin binding sites, placed at the interface between the EF5 loop the G helix and the EF4 loop. We show that Sorcin cellular localization changes upon doxorubicin treatment, an indication that the protein responds to doxorubicin and it presumably binds the drug also inside the cell, soon after drug entrance. We also demonstrate that Sorcin is able to limit the toxic effects of the chemotherapeutic agent in the cell. In addition, Sorcin silencing increases cell death upon treatment with doxorubicin, increases the accumulation of doxorubicin in cell nucleus, decreases the expression of MDR1 and doxorubicin efflux via MDR1.

Binding of doxorubicin to Sorcin impairs cell death and increases drug resistance in cancer cells.,Genovese I, Fiorillo A, Ilari A, Masciarelli S, Fazi F, Colotti G Cell Death Dis. 2017 Jul 20;8(7):e2950. doi: 10.1038/cddis.2017.342. PMID:28726784<ref>PMID:28726784</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mra" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Colotti G]]
[[Category: Fiorillo A]]
[[Category: Genovese I]]
[[Category: Ilari A]]