|
|
| Line 4: |
Line 4: |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[5x5p]] 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=5X5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X5P FirstGlance]. <br> | | <table><tr><td colspan='2'>[[5x5p]] 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=5X5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X5P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NTA:NITRILOTRIACETIC+ACID'>NTA</scene>, <scene name='pdbligand=RU:RUTHENIUM+ION'>RU</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]] 2.7Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NTA:NITRILOTRIACETIC+ACID'>NTA</scene>, <scene name='pdbligand=RU:RUTHENIUM+ION'>RU</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=5x5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x5p OCA], [https://pdbe.org/5x5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x5p RCSB], [https://www.ebi.ac.uk/pdbsum/5x5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x5p 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=5x5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x5p OCA], [https://pdbe.org/5x5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x5p RCSB], [https://www.ebi.ac.uk/pdbsum/5x5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x5p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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>
| + | [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 == | | == 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.
| + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 29: |
Line 30: |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sun, H]] | + | [[Category: Sun H]] |
| - | [[Category: Wang, M]] | + | [[Category: Wang M]] |
| - | [[Category: Metal transport]]
| + | |
| - | [[Category: Nta]]
| + | |
| - | [[Category: Ruthenium]]
| + | |
| - | [[Category: Transferrin]]
| + | |
| Structural highlights
5x5p is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.7Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
TRFE_HUMAN Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:209300. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.[1] [2]
Function
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.
Publication Abstract from PubMed
Being identified with less toxic and generally showing selective effects for solid tumor metastases, ruthenium and osmium compounds are promising drug candidates for clinical uses. Human serum proteins, such as albumin and transferrin, play vital roles in the transportation and accumulation of ruthenium and osmium agents into target tissues. However, the molecular mechanism of how transferrin transport ruthenium and their osmium analogues at atomic level remains obscure. In this study, we uncovered that the cellular uptake of Os(3+) or Ru(3+) are not competed by Fe(3+). To unveil the molecular mechanism behind the phenomena, we report the first crystal structures of human serum transferrin (hTF) in complex with ruthenium and osmium compounds bound to the non-conserved residues on the surface of hTF without altering its overall conformation. As for Ru(3+) and Os(3+), these binding sites by descending affinity are: His14/His289, His349-350 ~ His578/Arg581. Ruthenium drugs and their osmium analogues preferentially bind to His14/His289 with bipyridine or imidazole ligands leaving. These binding sites on hTF surface are also available in human lactoferrin and some transferrin family member of other species. The presence of these binding sites makes the cellular uptake of Ru(3+) and Os(3+) less affected by Fe(3+), compare to Zr(4+) or Hf(4+). Collectively, these findings are critical for our understanding of the role of serum transferrin in cellular delivery of ruthenium and osmium anticancer agents.
Binding of ruthenium and osmium at noniron sites of transferrin accounts for their iron-independent cellular uptake.,Wang M, Wang H, Xu X, Lai TP, Zhou Y, Hao Q, Li H, Sun H J Inorg Biochem. 2022 Jun 2;234:111885. doi: 10.1016/j.jinorgbio.2022.111885. PMID:35690040[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beutler E, Gelbart T, Lee P, Trevino R, Fernandez MA, Fairbanks VF. Molecular characterization of a case of atransferrinemia. Blood. 2000 Dec 15;96(13):4071-4. PMID:11110675
- ↑ Knisely AS, Gelbart T, Beutler E. Molecular characterization of a third case of human atransferrinemia. Blood. 2004 Oct 15;104(8):2607. PMID:15466165 doi:10.1182/blood-2004-05-1751
- ↑ Wang M, Wang H, Xu X, Lai TP, Zhou Y, Hao Q, Li H, Sun H. Binding of ruthenium and osmium at noniron sites of transferrin accounts for their iron-independent cellular uptake. J Inorg Biochem. 2022 Jun 2;234:111885. doi: 10.1016/j.jinorgbio.2022.111885. PMID:35690040 doi:http://dx.doi.org/10.1016/j.jinorgbio.2022.111885
|
