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2pmv

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[[Image:2pmv.gif|left|200px]]<br /><applet load="2pmv" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pmv, resolution 2.60&Aring;" />
 
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'''Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution'''<br />
 
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==Overview==
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==Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution==
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The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was, determined at 2.6-A resolution. The overall fold of the molecule is that, of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is, bound at the interface of the domains in a base-on conformation., Surprisingly, two full-length molecules, each comprising an alpha- and a, beta-domain and one Cbl, and two truncated molecules with only an alpha-, domain are present in the same asymmetric unit. The environment around Cbl, is dominated by uncharged residues, and the sixth coordinate position of, Co(2+) is empty. A detailed comparison between the IF-B12 complex and, another Cbl transport protein complex, trans-Cbl-B12, has been made. The, pH effect on the binding of Cbl analogues in transport proteins is, analyzed. A possible basis for the lack of interchangeability of human and, rat IF receptors is presented.
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<StructureSection load='2pmv' size='340' side='right'caption='[[2pmv]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pmv]] is a 4 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=2PMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PMV FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2pmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pmv OCA], [https://pdbe.org/2pmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pmv RCSB], [https://www.ebi.ac.uk/pdbsum/2pmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pmv ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN]] Defects in GIF are the cause of hereditary intrinsic factor deficiency (IFD) [MIM:[https://omim.org/entry/261000 261000]]; also known as congenital pernicious anemia. IFD is an autosomal recessive disorder characterized by megaloblastic anemia.<ref>PMID:15738392</ref>
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== Function ==
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[[https://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN]] Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.
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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/pm/2pmv_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=2pmv 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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The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.
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==About this Structure==
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Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.,Mathews FS, Gordon MM, Chen Z, Rajashankar KR, Ealick SE, Alpers DH, Sukumar N Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17311-6. Epub 2007 Oct 22. PMID:17954916<ref>PMID:17954916</ref>
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2PMV 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 <scene name='pdbligand=B12:'>B12</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PMV 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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Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-A resolution., Mathews FS, Gordon MM, Chen Z, Rajashankar KR, Ealick SE, Alpers DH, Sukumar N, Proc Natl Acad Sci U S A. 2007 Oct 22;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17954916 17954916]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2pmv" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Alpers, D.H.]]
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<references/>
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[[Category: Chen, Z.]]
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__TOC__
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[[Category: Ealick, S.E.]]
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</StructureSection>
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[[Category: Gordon, M.M.]]
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[[Category: Human]]
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[[Category: Mathews, F.S.]]
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[[Category: Large Structures]]
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[[Category: Rajashankar, K.R.]]
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[[Category: Alpers, D H]]
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[[Category: Sukumar, N.]]
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[[Category: Chen, Z]]
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[[Category: B12]]
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[[Category: Ealick, S E]]
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[[Category: cobalamin transport protein alpha6-alpha6 motif two domain protein]]
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[[Category: Gordon, M M]]
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[[Category: transport protein]]
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[[Category: Mathews, F S]]
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[[Category: Rajashankar, K R]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:19:52 2008''
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[[Category: Sukumar, N]]
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[[Category: Cobalamin transport protein alpha6-alpha6 motif two domain protein]]
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[[Category: Transport protein]]

Current revision

Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution

PDB ID 2pmv

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