|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2bb5' size='340' side='right'caption='[[2bb5]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='2bb5' size='340' side='right'caption='[[2bb5]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bb5]] is a 2 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=2BB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BB5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bb5]] is a 2 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=2BB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BB5 FirstGlance]. <br> |
| - | </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></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]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bb6|2bb6]], [[2bbc|2bbc]]</div></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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TCN2, TC2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2bb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bb5 OCA], [https://pdbe.org/2bb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bb5 RCSB], [https://www.ebi.ac.uk/pdbsum/2bb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bb5 ProSAT]</span></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=2bb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bb5 OCA], [https://pdbe.org/2bb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bb5 RCSB], [https://www.ebi.ac.uk/pdbsum/2bb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bb5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN]] Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:[https://omim.org/entry/275350 275350]]. This results in various forms of anemia.
| + | [https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN] Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:[https://omim.org/entry/275350 275350]. This results in various forms of anemia. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN]] Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.
| + | [https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN] Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 36: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fedosov, S N]] | + | [[Category: Fedosov SN]] |
| - | [[Category: Garau, G]] | + | [[Category: Garau G]] |
| - | [[Category: Geremia, S]] | + | [[Category: Geremia S]] |
| - | [[Category: Petersen, T E]] | + | [[Category: Petersen TE]] |
| - | [[Category: Randaccio, L]] | + | [[Category: Randaccio L]] |
| - | [[Category: Wuerges, J]] | + | [[Category: Wuerges J]] |
| - | [[Category: Alpha_6 - alpha_6 barrel]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
TCO2_HUMAN Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:275350. This results in various forms of anemia.
Function
TCO2_HUMAN Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.
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
Cobalamin (Cbl, vitamin B(12)) serves for two essential cofactors in mammals. The pathway for its intestinal absorption, plasma transport, and cellular uptake uses cell surface receptors and three Cbl-transporting proteins, haptocorrin, intrinsic factor, and transcobalamin (TC). We present the structure determination of a member of the mammalian Cbl-transporter family. The crystal structures of recombinant human and bovine holo-TCs reveal a two-domain architecture, with an N-terminal alpha(6)-alpha(6) barrel and a smaller C-terminal domain. One Cbl molecule in base-on conformation is buried inside the domain interface. Structural data combined with previous binding assays indicate a domain motion in the first step of Cbl binding. In a second step, the weakly coordinated ligand H(2)O at the upper axial side of added H(2)O-Cbl is displaced by a histidine residue of the alpha(6)-alpha(6) barrel. Analysis of amino acid conservation on TC's surface in orthologous proteins suggests the location of the TC-receptor-recognition site in an extended region on the alpha(6)-alpha(6) barrel. The TC structure allows for the mapping of sites of amino acid variation due to polymorphisms of the human TC gene. Structural information is used to predict the overall fold of haptocorrin and intrinsic factor and permits a rational approach to the design of new Cbl-based bioconjugates for diagnostic or therapeutic drug delivery.
Structural basis for mammalian vitamin B12 transport by transcobalamin.,Wuerges J, Garau G, Geremia S, Fedosov SN, Petersen TE, Randaccio L Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4386-91. Epub 2006 Mar 14. PMID:16537422[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wuerges J, Garau G, Geremia S, Fedosov SN, Petersen TE, Randaccio L. Structural basis for mammalian vitamin B12 transport by transcobalamin. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4386-91. Epub 2006 Mar 14. PMID:16537422
|
