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[[Image:1l5t.jpg|left|200px]]
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{{STRUCTURE_1l5t|  PDB=1l5t  |  SCENE=  }}
'''Crystal Structure of a Domain-Opened Mutant (R121D) of the Human Lactoferrin N-lobe Refined From a Merohedrally-Twinned Crystal Form.'''


==Crystal Structure of a Domain-Opened Mutant (R121D) of the Human Lactoferrin N-lobe Refined From a Merohedrally-Twinned Crystal Form.==
<StructureSection load='1l5t' size='340' side='right'caption='[[1l5t]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1l5t]] is a 2 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=1L5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L5T 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]] 3&#8491;</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=1l5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l5t OCA], [https://pdbe.org/1l5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l5t RCSB], [https://www.ebi.ac.uk/pdbsum/1l5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l5t 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/l5/1l5t_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1l5t ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human lactoferrin is an iron-binding protein with a bilobal structure. Each lobe contains a high-affinity binding site for a single Fe(3+) ion and an associated CO(3)(2-) ion. Although iron binds very tightly, it can be released at low pH, with an accompanying conformational change in which the two domains move apart. The Arg121Asp (R121D) mutant of the N-lobe half-molecule of human lactoferrin was constructed in order to test whether the Asp121 side chain could substitute for the CO(3)(2-) ion at the iron-binding site. The R121D mutant protein was crystallized in its apo form as it lost iron during crystallization. The crystals were also merohedrally twinned, with a twin fraction close to 0.5. Starting from the initial molecular-replacement solution [Breyer et al. (1999), Acta Cryst. D55, 129-138], the structure has been refined at 3.0 A resolution to an R factor of 13.9% (R(free) of 19.9%). Despite the moderate resolution, the high solvent content and non-crystallographic symmetry contributed to electron-density maps of excellent quality. Weakened iron binding by the R121D mutant is explained by occlusion of the anion-binding site by the Asp side chain. The opening of the two domains in the apoR121D structure (a rotation of 54 degrees ) closely matches that of the N-lobe in full-length lactoferrin, showing that the extent of the conformational change depends on properties inherent to the N-lobe. Differences in the C-terminal portion of the N-lobe (residues 321-332) for apoR121D relative to the closed wild-type iron-bound structure point to the importance of this region in stabilizing the open form.


==Overview==
Structure of a domain-opened mutant (R121D) of the human lactoferrin N-lobe refined from a merohedrally twinned crystal form.,Jameson GB, Anderson BF, Breyer WA, Day CL, Tweedie JW, Baker EN Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6 Pt 2):955-62. Epub, 2002 May 29. PMID:12037297<ref>PMID:12037297</ref>
Human lactoferrin is an iron-binding protein with a bilobal structure. Each lobe contains a high-affinity binding site for a single Fe(3+) ion and an associated CO(3)(2-) ion. Although iron binds very tightly, it can be released at low pH, with an accompanying conformational change in which the two domains move apart. The Arg121Asp (R121D) mutant of the N-lobe half-molecule of human lactoferrin was constructed in order to test whether the Asp121 side chain could substitute for the CO(3)(2-) ion at the iron-binding site. The R121D mutant protein was crystallized in its apo form as it lost iron during crystallization. The crystals were also merohedrally twinned, with a twin fraction close to 0.5. Starting from the initial molecular-replacement solution [Breyer et al. (1999), Acta Cryst. D55, 129-138], the structure has been refined at 3.0 A resolution to an R factor of 13.9% (R(free) of 19.9%). Despite the moderate resolution, the high solvent content and non-crystallographic symmetry contributed to electron-density maps of excellent quality. Weakened iron binding by the R121D mutant is explained by occlusion of the anion-binding site by the Asp side chain. The opening of the two domains in the apoR121D structure (a rotation of 54 degrees ) closely matches that of the N-lobe in full-length lactoferrin, showing that the extent of the conformational change depends on properties inherent to the N-lobe. Differences in the C-terminal portion of the N-lobe (residues 321-332) for apoR121D relative to the closed wild-type iron-bound structure point to the importance of this region in stabilizing the open form.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1L5T is a [[Single protein]] structure of 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=1L5T OCA].
</div>
<div class="pdbe-citations 1l5t" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure of a domain-opened mutant (R121D) of the human lactoferrin N-lobe refined from a merohedrally twinned crystal form., Jameson GB, Anderson BF, Breyer WA, Day CL, Tweedie JW, Baker EN, Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6 Pt 2):955-62. Epub, 2002 May 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12037297 12037297]
*[[Lactoferrin|Lactoferrin]]
[[Category: Diferric-transferrin reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Anderson, B F.]]
[[Category: Anderson BF]]
[[Category: Baker, E N.]]
[[Category: Baker EN]]
[[Category: Breyer, W A.]]
[[Category: Breyer WA]]
[[Category: Jameson, G B.]]
[[Category: Jameson GB]]
[[Category: Tweedie, J W.]]
[[Category: Tweedie JW]]
[[Category: Glycoprotein]]
[[Category: Iron transport]]
[[Category: Iron-release]]
[[Category: Lactoferrin]]
[[Category: N-lobe]]
[[Category: Twinning]]
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