View source for 1dtg


==HUMAN TRANSFERRIN N-LOBE MUTANT H249E==
<StructureSection load='1dtg' size='340' side='right'caption='[[1dtg]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dtg]] 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=1DTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DTG 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=1dtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtg OCA], [https://pdbe.org/1dtg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dtg RCSB], [https://www.ebi.ac.uk/pdbsum/1dtg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dtg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:[https://omim.org/entry/209300 209300]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.<ref>PMID:11110675</ref> <ref>PMID:15466165</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
== 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/dt/1dtg_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=1dtg ConSurf].
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== Publication Abstract from PubMed ==
Serum transferrin is the major iron transport protein in humans. Its function depends on its ability to bind iron with very high affinity, yet to release this bound iron at the lower intracellular pH. Possible explanations for the release of iron from transferrin at low pH include protonation of a histidine ligand and the existence of a pH-sensitive "trigger" involving a hydrogen-bonded pair of lysines in the N-lobe of transferrin. We have determined the crystal structure of the His249Glu mutant of the N-lobe half-molecule of human transferrin and compared its iron-binding properties with those of the wild-type protein and other mutants. The crystal structure, determined at 2.4 A resolution (R-factor 19.8%, R(free) 29.4%), shows that Glu 249 is directly bound to iron, in place of the His ligand, and that a local movement of Lys 296 has broken the dilysine interaction. Despite the loss of this potentially pH-sensitive interaction, the H249E mutant is only slightly more acid-stable than wild-type and releases iron slightly faster. We conclude that the loss of the dilysine interaction does make the protein more acid stable but that this is counterbalanced by the replacement of a neutral ligand (His) by a negatively charged one (Glu), thus disrupting the electroneutrality of the binding site.

Mutation of the iron ligand His 249 to Glu in the N-lobe of human transferrin abolishes the dilysine "trigger" but does not significantly affect iron release.,MacGillivray RT, Bewley MC, Smith CA, He QY, Mason AB, Woodworth RC, Baker EN Biochemistry. 2000 Feb 15;39(6):1211-6. PMID:10684598<ref>PMID:10684598</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1dtg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transferrin 3D structures|Transferrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bewley MC]]
[[Category: He QY]]
[[Category: MacGillivray RT]]
[[Category: Mason AB]]
[[Category: Smith CA]]