1ryo
From Proteopedia
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|PDB= 1ryo |SIZE=350|CAPTION= <scene name='initialview01'>1ryo</scene>, resolution 1.20Å | |PDB= 1ryo |SIZE=350|CAPTION= <scene name='initialview01'>1ryo</scene>, resolution 1.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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.ebi.ac.uk/pdbsum/1ryo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ryo RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Atransferrinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190000 190000]], Iron deficiency anemia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190000 190000]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Halbrooks, P J.]] | [[Category: Halbrooks, P J.]] | ||
[[Category: Mason, A B.]] | [[Category: Mason, A B.]] | ||
| - | [[Category: FE]] | ||
| - | [[Category: OXL]] | ||
[[Category: iron transport]] | [[Category: iron transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:34:50 2008'' |
Revision as of 20:34, 30 March 2008
| |||||||
| , resolution 1.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | TF (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human serum transferrin, N-lobe bound with oxalate
Contents |
Overview
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.
Disease
Known disease associated with this structure: Atransferrinemia OMIM:[190000], Iron deficiency anemia, susceptibility to OMIM:[190000]
About this Structure
1RYO is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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