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1nep

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(New page: 200px<br /><applet load="1nep" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nep, resolution 1.70&Aring;" /> '''Crystal Structure An...)
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[[Image:1nep.gif|left|200px]]<br /><applet load="1nep" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nep, resolution 1.70&Aring;" />
 
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'''Crystal Structure Analysis of the Bovine NPC2 (Niemann-Pick C2) Protein'''<br />
 
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==Overview==
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==Crystal Structure Analysis of the Bovine NPC2 (Niemann-Pick C2) Protein==
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Niemann-Pick disease type C2 (NP-C2) is a fatal hereditary disease, characterized by accumulation of low-density lipoprotein-derived, cholesterol in lysosomes. Here we report the 1.7-A resolution crystal, structure of the cholesterol-binding protein deficient in this disease, NPC2, and the characterization of its ligand binding properties. Human, NPC2 binds the cholesterol analog dehydroergosterol with submicromolar, affinity at both acidic and neutral pH. NPC2 has an Ig-like fold, stabilized by three disulfide bonds. The structure of the bovine protein, reveals a loosely packed region penetrating from the surface into the, hydrophobic core that forms adjacent small cavities with a total volume of, approximately 160 A(3). We propose that this region represents the, incipient cholesterol-binding site that dilates to accommodate an, approximately 740-A(3) cholesterol molecule.
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<StructureSection load='1nep' size='340' side='right'caption='[[1nep]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1nep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NEP FirstGlance]. <br>
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1NEP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with NAG and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NEP OCA].
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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]] 1.7&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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==Reference==
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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=1nep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nep OCA], [https://pdbe.org/1nep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nep RCSB], [https://www.ebi.ac.uk/pdbsum/1nep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nep ProSAT]</span></td></tr>
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Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease., Friedland N, Liou HL, Lobel P, Stock AM, Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2512-7. Epub 2003 Feb 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12591954 12591954]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NPC2_BOVIN NPC2_BOVIN] Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.<ref>PMID:18823126</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/ne/1nep_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=1nep ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Friedland, N.]]
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[[Category: Friedland N]]
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[[Category: Liou, H.L.]]
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[[Category: Liou H-L]]
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[[Category: Lobel, P.]]
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[[Category: Lobel P]]
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[[Category: Stock, A.M.]]
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[[Category: Stock AM]]
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[[Category: NAG]]
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[[Category: PO4]]
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[[Category: bnpc2]]
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[[Category: cholesterol]]
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[[Category: ldl]]
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[[Category: niemann-pick c2]]
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[[Category: npc2]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:11:43 2007''
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Current revision

Crystal Structure Analysis of the Bovine NPC2 (Niemann-Pick C2) Protein

PDB ID 1nep

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