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1ryo

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Revision as of 06:41, 6 January 2015

Human serum transferrin, N-lobe bound with oxalate

Structural highlights

1ryo 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.
Ligands:	,
Gene:	TF (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

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

A unique feature of the mechanism of iron binding to the transferrin (TF) family is the synergistic relationship between metal binding and anion binding. Little or no iron will bind to the protein without concomitant binding of an anion, physiologically identified as carbonate. Substitution of oxalate for carbonate produces no significant changes in polypeptide folding or domain orientation in the N-lobe of human serum TF (hTF) as revealed by our 1.2A structure. The oxalate is able to bind to the iron in a symmetric bidentate fashion, which, combined with the low pK(a) of the oxalate anion, makes iron displacement more difficult as documented by both iron release kinetic and equilibrium data. Characterization of an N-lobe in which the arginine at position 124 is mutated to alanine reveals that the stabilizing effect of oxalate is even greater in this mutant and nearly cancels the destabilizing effect of the mutation. Importantly, incorporation of oxalate as the synergistic anion appears to completely inhibit removal of iron from recombinant full-length hTF by HeLa S(3) cells, strongly indicating that oxalate also replaces carbonate in the C-lobe to form a stable complex. Kinetic studies confirm this claim. The combination of structural and functional data provides a coherent delineation of the effect of oxalate binding on hTF and rationalizes the results of many previous studies. In the context of iron uptake by cells, substitution of carbonate by oxalate effectively locks the iron into each lobe of hTF, thereby interfering with normal iron metabolism.

The oxalate effect on release of iron from human serum transferrin explained.,Halbrooks PJ, Mason AB, Adams TE, Briggs SK, Everse SJ J Mol Biol. 2004 May 21;339(1):217-26. PMID:15123433^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Halbrooks PJ, Mason AB, Adams TE, Briggs SK, Everse SJ. The oxalate effect on release of iron from human serum transferrin explained. J Mol Biol. 2004 May 21;339(1):217-26. PMID:15123433 doi:10.1016/j.jmb.2004.03.049

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ryo"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1ryo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RYO FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ryo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ryo RCSB], [http://www.ebi.ac.uk/pdbsum/1ryo PDBsum]</span></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=1ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ryo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ryo RCSB], [http://www.ebi.ac.uk/pdbsum/1ryo PDBsum]</span></td></tr>
-<table>
+</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>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Adams, T E.]]
+[[Category: Adams, T E]]
-[[Category: Briggs, S K.]]
+[[Category: Briggs, S K]]
-[[Category: Everse, S J.]]
+[[Category: Everse, S J]]
-[[Category: Halbrooks, P J.]]
+[[Category: Halbrooks, P J]]
-[[Category: Mason, A B.]]
+[[Category: Mason, A B]]
 [[Category: Iron transport]]
 [[Category: Metal transport]]

1ryo

From Proteopedia

Revision as of 06:41, 6 January 2015

Human serum transferrin, N-lobe bound with oxalate

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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