1h44: Difference between revisions
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[[Image: | ==R210L N-TERMINAL LOBE HUMAN LACTOFERRIN== | ||
<StructureSection load='1h44' size='340' side='right' caption='[[1h44]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1h44]] 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=1H44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H44 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b0l|1b0l]], [[1bka|1bka]], [[1cb6|1cb6]], [[1dsn|1dsn]], [[1eh3|1eh3]], [[1fck|1fck]], [[1h43|1h43]], [[1h45|1h45]], [[1hse|1hse]], [[1l5t|1l5t]], [[1lcf|1lcf]], [[1lct|1lct]], [[1lfg|1lfg]], [[1lfh|1lfh]], [[1lfi|1lfi]], [[1lgb|1lgb]], [[1vfd|1vfd]], [[1vfe|1vfe]]</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=1h44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h44 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h44 RCSB], [http://www.ebi.ac.uk/pdbsum/1h44 PDBsum]</span></td></tr> | |||
<table> | |||
== 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/h4/1h44_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mammalian iron-binding proteins lactoferrin (Lf) and transferrin (Tf) bind iron very tightly, but reversibly. Despite homologous structures and essentially identical iron binding sites, Tf begins to release iron at pH 6.0, whereas Lf retains iron to pH approximately 3.5. This difference in iron retention gives the two proteins different biological roles. Two lysine residues, Lys 206 and Lys 296, which form a hydrogen-bonded dilysine pair in human Tf, have been shown to strongly influence iron release from the N-lobe. The equivalent residues in human Lf are Arg 210 and Lys 301, and we have here mutated Arg 210 in the N-lobe half-molecule of human lactoferrin, Lf(N), to probe its role in iron release. The Lf(N) mutants R210G, R210E, and R210L were expressed, purified, and crystallized, and their crystal structures were determined and refined at resolutions of 1.95 A (R210G), 2.2 A (R210E), and 2.0 A (R210L). The overall structures are very similar to that of wild-type Lf(N), but with small differences in domain orientations. In each of the mutants, however, Lys 301 (equivalent to Lys 296 in Tf) changes its conformation to fill the space occupied by Arg 210 Neta2 in wild-type Lf(N), interacting with the two tyrosine ligands Tyr 92 and Tyr 192. By comparison with other Lf and Tf structures, we conclude that Lys 301 (or Lys 296 in Tf) only occupies this site when residue 210 (206 in Tf) is nonpositive (neutral as in R210G and R210L or negative as in R210E). Thus, Lys 206 in the Tf dilysine pair is identified as having a depressed pK(a). Three specific sites are variably occupied by polar groups in the Lf mutants and other Lf and Tf proteins, and when coupled with iron-release data, these give new insights into the factors that most influence iron retention at low pH. | |||
"Dilysine trigger" in transferrins probed by mutagenesis of lactoferrin: crystal structures of the R210G, R210E, and R210L mutants of human lactoferrin.,Peterson NA, Arcus VL, Anderson BF, Tweedie JW, Jameson GB, Baker EN Biochemistry. 2002 Dec 3;41(48):14167-75. PMID:12450380<ref>PMID:12450380</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Lactoferrin|Lactoferrin]] | *[[Lactoferrin|Lactoferrin]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Anderson, B F.]] | [[Category: Anderson, B F.]] | ||
Revision as of 14:19, 28 September 2014
R210L N-TERMINAL LOBE HUMAN LACTOFERRINR210L N-TERMINAL LOBE HUMAN LACTOFERRIN
Structural highlights
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 PubMedThe mammalian iron-binding proteins lactoferrin (Lf) and transferrin (Tf) bind iron very tightly, but reversibly. Despite homologous structures and essentially identical iron binding sites, Tf begins to release iron at pH 6.0, whereas Lf retains iron to pH approximately 3.5. This difference in iron retention gives the two proteins different biological roles. Two lysine residues, Lys 206 and Lys 296, which form a hydrogen-bonded dilysine pair in human Tf, have been shown to strongly influence iron release from the N-lobe. The equivalent residues in human Lf are Arg 210 and Lys 301, and we have here mutated Arg 210 in the N-lobe half-molecule of human lactoferrin, Lf(N), to probe its role in iron release. The Lf(N) mutants R210G, R210E, and R210L were expressed, purified, and crystallized, and their crystal structures were determined and refined at resolutions of 1.95 A (R210G), 2.2 A (R210E), and 2.0 A (R210L). The overall structures are very similar to that of wild-type Lf(N), but with small differences in domain orientations. In each of the mutants, however, Lys 301 (equivalent to Lys 296 in Tf) changes its conformation to fill the space occupied by Arg 210 Neta2 in wild-type Lf(N), interacting with the two tyrosine ligands Tyr 92 and Tyr 192. By comparison with other Lf and Tf structures, we conclude that Lys 301 (or Lys 296 in Tf) only occupies this site when residue 210 (206 in Tf) is nonpositive (neutral as in R210G and R210L or negative as in R210E). Thus, Lys 206 in the Tf dilysine pair is identified as having a depressed pK(a). Three specific sites are variably occupied by polar groups in the Lf mutants and other Lf and Tf proteins, and when coupled with iron-release data, these give new insights into the factors that most influence iron retention at low pH. "Dilysine trigger" in transferrins probed by mutagenesis of lactoferrin: crystal structures of the R210G, R210E, and R210L mutants of human lactoferrin.,Peterson NA, Arcus VL, Anderson BF, Tweedie JW, Jameson GB, Baker EN Biochemistry. 2002 Dec 3;41(48):14167-75. PMID:12450380[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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