1hse
From Proteopedia
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| - | [[Image:1hse.gif|left|200px]]<br /><applet load="1hse" size=" | + | [[Image:1hse.gif|left|200px]]<br /><applet load="1hse" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hse, resolution 2.2Å" /> | caption="1hse, resolution 2.2Å" /> | ||
'''H253M N TERMINAL LOBE OF HUMAN LACTOFERRIN'''<br /> | '''H253M N TERMINAL LOBE OF HUMAN LACTOFERRIN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HSE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FE and CO3 as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=S1:Metal And Anion Binding Site'>S1</scene>. Full crystallographic information is available from [http:// | + | 1HSE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FE:'>FE</scene> and <scene name='pdbligand=CO3:'>CO3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=S1:Metal+And+Anion+Binding+Site'>S1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HSE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferrin]] | [[Category: transferrin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:50:14 2008'' |
Revision as of 07:50, 3 February 2008
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H253M N TERMINAL LOBE OF HUMAN LACTOFERRIN
Contents |
Overview
The contribution of the conserved His ligand to iron binding in, transferrins has been addressed by site-directed mutagenesis and X-ray, crystallographic analysis. His 253 in the N-terminal half-molecule of, human lactoferrin, LfN (residues 1-333), has been changed to Gly, Ala, Pro, Thr, Leu, Phe, Met, Tyr, Glu, Gln, and Cys by, oligonucleotide-directed mutagenesis. The proteins have been expressed in, baby hamster kidney cells, at high levels, and purified. The results show, that the His ligand is essential for the stability of the iron binding, site. All of the substitutions destabilized iron binding irrespective of, whether the replacements were potential iron ligands or not. Iron was lost, below pH approximately 6 for the Cys, Glu, and Tyr mutants and below pH 7, or higher for the others, compared with pH 5.0 for LfN. The, destabilization is attributed to both steric and electronic effects. The, importance of electronic effects has been shown by the crystal structure, of the H253M mutant, which has been determined at an effective resolution, of 2.5 A and refined to a final R factor of 0.173. The iron atom is, changed from six-coordinate to five-coordinate; the Met 253 side chain is, not bound to iron even though there appears to be no steric barrier. This, is attributed to the poorer affinity of the thioether ligand for Fe(III), compared with imidazole nitrogen. The decreased stability of the iron, binding is attributed solely to the loss of the His ligand as the protein, conformation and interdomain interactions are unchanged.
Disease
Known disease associated with this structure: Deafness, autosomal dominant 1 OMIM:[602121]
About this Structure
1HSE is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Mutagenesis of the histidine ligand in human lactoferrin: iron binding properties and crystal structure of the histidine-253-->methionine mutant., Nicholson H, Anderson BF, Bland T, Shewry SC, Tweedie JW, Baker EN, Biochemistry. 1997 Jan 14;36(2):341-6. PMID:9003186
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