View source for 6ctc


==Crystal structure of human transferrin bound to Triferic FPC iron pyrophosphate==
<StructureSection load='6ctc' size='340' side='right' caption='[[6ctc]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ctc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CTC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TF, PRO1400 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ctc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ctc OCA], [http://pdbe.org/6ctc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ctc RCSB], [http://www.ebi.ac.uk/pdbsum/6ctc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ctc ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN]] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:[http://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 ==
[[http://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. 
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== Publication Abstract from PubMed ==
There are several options available for intravenous application of iron supplements, but they all have a similar structure:-an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.

Ferric pyrophosphate citrate: interactions with transferrin.,Pratt R, Handelman GJ, Edwards TE, Gupta A Biometals. 2018 Oct 11. pii: 10.1007/s10534-018-0142-2. doi:, 10.1007/s10534-018-0142-2. PMID:30311019<ref>PMID:30311019</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Edwards, T E]]
[[Category: Pratt, R]]
[[Category: Blood]]
[[Category: Fpc]]
[[Category: Iron]]
[[Category: Metal transport]]
[[Category: Plasma]]
[[Category: Pyrophosphate]]
[[Category: Transferrin]]
[[Category: Transfusion]]
[[Category: Triferic iron]]