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2cbz

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(New page: 200px<br /> <applet load="2cbz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cbz, resolution 1.50&Aring;" /> '''STRUCTURE OF THE HU...)
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[[Image:2cbz.gif|left|200px]]<br />
 
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<applet load="2cbz" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2cbz, resolution 1.50&Aring;" />
 
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'''STRUCTURE OF THE HUMAN MULTIDRUG RESISTANCE PROTEIN 1 NUCLEOTIDE BINDING DOMAIN 1'''<br />
 
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==Overview==
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==Structure of the human Multidrug Resistance Protein 1 Nucleotide Binding Domain 1==
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Human multidrug resistance protein 1 (MRP1) is a membrane protein that, belongs to the ATP-binding cassette (ABC) superfamily of transport, proteins. MRP1 contributes to chemotherapy failure by exporting a wide, range of anti-cancer drugs when over expressed in the plasma membrane of, cells. Here, we report the first high-resolution crystal structure of, human MRP1-NBD1. Drug efflux requires energy resulting from hydrolysis of, ATP by nucleotide binding domains (NBDs). Contrary to the prokaryotic, NBDs, the extremely low intrinsic ATPase activity of isolated MRP1-NBDs, allowed us to obtain the structure of wild-type NBD1 in complex with, Mg2+/ATP. The structure shows that MRP1-NBD1 adopts a canonical fold, but, reveals an unexpected non-productive conformation of the catalytic site, ... [[http://ispc.weizmann.ac.il/pmbin/getpm?16697012 (full description)]]
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<StructureSection load='2cbz' size='340' side='right'caption='[[2cbz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2cbz]] 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=2CBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBZ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<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=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbz OCA], [https://pdbe.org/2cbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cbz RCSB], [https://www.ebi.ac.uk/pdbsum/2cbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MRP1_HUMAN MRP1_HUMAN] Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.<ref>PMID:10064732</ref> <ref>PMID:11114332</ref> <ref>PMID:16230346</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cb/2cbz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cbz ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human multidrug resistance protein 1 (MRP1) is a membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 contributes to chemotherapy failure by exporting a wide range of anti-cancer drugs when over expressed in the plasma membrane of cells. Here, we report the first high-resolution crystal structure of human MRP1-NBD1. Drug efflux requires energy resulting from hydrolysis of ATP by nucleotide binding domains (NBDs). Contrary to the prokaryotic NBDs, the extremely low intrinsic ATPase activity of isolated MRP1-NBDs allowed us to obtain the structure of wild-type NBD1 in complex with Mg2+/ATP. The structure shows that MRP1-NBD1 adopts a canonical fold, but reveals an unexpected non-productive conformation of the catalytic site, providing an explanation for the low intrinsic ATPase activity of NBD1 and new hypotheses on the cooperativity of ATPase activity between NBD1 and NBD2 upon heterodimer formation.
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==About this Structure==
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Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site.,Ramaen O, Leulliot N, Sizun C, Ulryck N, Pamlard O, Lallemand JY, Tilbeurgh H, Jacquet E J Mol Biol. 2006 Jun 16;359(4):940-9. Epub 2006 May 2. PMID:16697012<ref>PMID:16697012</ref>
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2CBZ is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with MG and ATP as [[http://en.wikipedia.org/wiki/ligands ligands]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CBZ OCA]].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site., Ramaen O, Leulliot N, Sizun C, Ulryck N, Pamlard O, Lallemand JY, Tilbeurgh H, Jacquet E, J Mol Biol. 2006 Jun 16;359(4):940-9. Epub 2006 May 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16697012 16697012]
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</div>
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<div class="pdbe-citations 2cbz" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Jacquet, E.]]
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[[Category: Jacquet E]]
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[[Category: Lallemand, J.Y.]]
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[[Category: Lallemand J-Y]]
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[[Category: Leulliot, N.]]
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[[Category: Leulliot N]]
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[[Category: Pamlard, O.]]
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[[Category: Pamlard O]]
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[[Category: Ramaen, O.]]
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[[Category: Ramaen O]]
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[[Category: Sizun, C.]]
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[[Category: Sizun C]]
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[[Category: Tilbeurgh, H.Van.]]
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[[Category: Ulryck N]]
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[[Category: Ulryck, N.]]
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[[Category: Van Tilbeurgh H]]
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[[Category: ATP]]
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[[Category: MG]]
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[[Category: abc proteins]]
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[[Category: atp-binding]]
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[[Category: hydrolysis]]
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[[Category: mrp1/abcc1]]
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[[Category: nucleotide-binding domain]]
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[[Category: transport]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Oct 29 21:25:46 2007''
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Current revision

Structure of the human Multidrug Resistance Protein 1 Nucleotide Binding Domain 1

PDB ID 2cbz

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