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[[Image:2pmv.gif|left|200px]]<br /><applet load="2pmv" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2pmv, resolution 2.60&Aring;" />
'''Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution'''<br />


==Overview==
==Crystal Structure of Human Intrinsic Factor- Cobalamin Complex at 2.6 A Resolution==
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.
<StructureSection load='2pmv' size='340' side='right'caption='[[2pmv]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2pmv]] 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=2PMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PMV 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]] 2.6&#8491;</td></tr>
<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></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=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>
</table>
== Disease ==
[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>
== Function ==
[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/2pmv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==About this Structure==
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>
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].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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]
</div>
<div class="pdbe-citations 2pmv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Alpers, D.H.]]
[[Category: Alpers DH]]
[[Category: Chen, Z.]]
[[Category: Chen Z]]
[[Category: Ealick, S.E.]]
[[Category: Ealick SE]]
[[Category: Gordon, M.M.]]
[[Category: Gordon MM]]
[[Category: Mathews, F.S.]]
[[Category: Mathews FS]]
[[Category: Rajashankar, K.R.]]
[[Category: Rajashankar KR]]
[[Category: Sukumar, N.]]
[[Category: Sukumar N]]
[[Category: B12]]
[[Category: cobalamin transport protein alpha6-alpha6 motif two domain protein]]
[[Category: transport protein]]
 
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Retrieved from "https://proteopedia.org/2pmv"