View source for 1hse


==H253M N TERMINAL LOBE OF HUMAN LACTOFERRIN==
<StructureSection load='1hse' size='340' side='right'caption='[[1hse]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hse]] 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=1HSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HSE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=1hse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hse OCA], [https://pdbe.org/1hse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hse RCSB], [https://www.ebi.ac.uk/pdbsum/1hse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hse ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRFL_HUMAN TRFL_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref>   Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref>   Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref>   The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref>   Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hs/1hse_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hse ConSurf].
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== Publication Abstract from PubMed ==
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.

Mutagenesis of the histidine ligand in human lactoferrin: iron binding properties and crystal structure of the histidine-253--&gt;methionine mutant.,Nicholson H, Anderson BF, Bland T, Shewry SC, Tweedie JW, Baker EN Biochemistry. 1997 Jan 14;36(2):341-6. PMID:9003186<ref>PMID:9003186</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Lactoferrin|Lactoferrin]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Anderson BF]]
[[Category: Baker EN]]
[[Category: Nicholson H]]