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2cbz

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

Structural highlights

2cbz is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sjolinder M, Tornhamre S, Claesson HE, Hydman J, Lindgren J. Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1. J Lipid Res. 1999 Mar;40(3):439-46. PMID:10064732
↑ Robbiani DF, Finch RA, Jager D, Muller WA, Sartorelli AC, Randolph GJ. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell. 2000 Nov 22;103(5):757-68. PMID:11114332
↑ Conseil G, Deeley RG, Cole SP. Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1). J Biol Chem. 2006 Jan 6;281(1):43-50. Epub 2005 Oct 17. PMID:16230346 doi:http://dx.doi.org/10.1074/jbc.M510143200
↑ Ramaen O, Leulliot N, Sizun C, Ulryck N, Pamlard O, Lallemand JY, Tilbeurgh H, Jacquet E. Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site. J Mol Biol. 2006 Jun 16;359(4):940-9. Epub 2006 May 2. PMID:16697012 doi:http://dx.doi.org/10.1016/j.jmb.2006.04.005

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2cbz"

@@ Line 3: / Line 3: @@
 <StructureSection load='2cbz' size='340' side='right'caption='[[2cbz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2cbz]] is a 1 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=2CBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBZ FirstGlance]. <br>
+<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>
-</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=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</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>
+<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>
 <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>
 </table>
+== Function ==
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Jacquet, E]]
+[[Category: Jacquet E]]
-[[Category: Lallemand, J Y]]
+[[Category: Lallemand J-Y]]
-[[Category: Leulliot, N]]
+[[Category: Leulliot N]]
-[[Category: Pamlard, O]]
+[[Category: Pamlard O]]
-[[Category: Ramaen, O]]
+[[Category: Ramaen O]]
-[[Category: Sizun, C]]
+[[Category: Sizun C]]
-[[Category: Tilbeurgh, H van]]
+[[Category: Ulryck N]]
-[[Category: Ulryck, N]]
+[[Category: Van Tilbeurgh H]]
-[[Category: Abc protein]]
-[[Category: Atp-binding]]
-[[Category: Hydrolysis]]
-[[Category: Mrp1/abcc1]]
-[[Category: Nucleotide-binding domain]]
-[[Category: Transport]]

2cbz

From Proteopedia

Current revision

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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