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==Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin== | ==Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin== | ||
<StructureSection load='1iwh' size='340' side='right' caption='[[1iwh]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='1iwh' size='340' side='right'caption='[[1iwh]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1iwh]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1iwh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IWH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PEM:2-[P-[2-P-CHLOROBENZAMIDO)ETHYL]PHENOXY]-2-METHYLPROPIONIC+ACID'>PEM</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=1iwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iwh OCA], [https://pdbe.org/1iwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iwh RCSB], [https://www.ebi.ac.uk/pdbsum/1iwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iwh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HBA_HORSE HBA_HORSE] Involved in oxygen transport from the lung to the various peripheral tissues. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iw/1iwh_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iw/1iwh_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=1iwh ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 35: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Equus caballus]] | [[Category: Equus caballus]] | ||
[[Category: Miura | [[Category: Large Structures]] | ||
[[Category: Park | [[Category: Miura S]] | ||
[[Category: Shibayama | [[Category: Park S-Y]] | ||
[[Category: Tame | [[Category: Shibayama N]] | ||
[[Category: Yonetani | [[Category: Tame JRH]] | ||
[[Category: Yonetani T]] | |||
Latest revision as of 02:38, 28 December 2023
Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State HemoglobinCrystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin
Structural highlights
FunctionHBA_HORSE Involved in oxygen transport from the lung to the various peripheral tissues. 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 PubMedBezafibrate, an antilipidemic drug, is known as a potent allosteric effector of hemoglobin. The previously proposed mechanism for the allosteric potency of this drug was that it stabilizes and constrains the T-state of hemoglobin by specifically binding to the large central cavity of the T-state. Here we report a new allosteric binding site of fully liganded R-state hemoglobin for this drug. The high resolution crystal structure of horse carbonmonoxyhemoglobin in complex with bezafibrate reveals that the bezafibrate molecule lies near the surface of the E-helix of each alpha subunit and the complex maintains the quaternary structure of the R-state. Binding is caused by the close fit of bezafibrate into the binding pocket, which is composed of some hydrophobic residues and the heme edge, suggesting the importance of hydrophobic interactions. Upon binding of bezafibrate, the distance between Fe and the N epsilon(2) of distal His E7(alpha 58) is shortened by 0.22 A in the alpha subunit, whereas no significant structural changes are transmitted to the beta subunit. Oxygen equilibrium studies of R-state-locked hemoglobin with bezafibrate in a wet porous sol-gel indicate that bezafibrate selectively lowers the oxygen affinity of one type of subunit within the R-state, consistent with the structural data. These results disclose a new allosteric mechanism of bezafibrate and offer the first demonstration of how the allosteric effector interacts with R-state hemoglobin. Crystal structure of horse carbonmonoxyhemoglobin-bezafibrate complex at 1.55-A resolution. A novel allosteric binding site in R-state hemoglobin.,Shibayama N, Miura S, Tame JR, Yonetani T, Park SY J Biol Chem. 2002 Oct 11;277(41):38791-6. Epub 2002 Jul 16. PMID:12122004[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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