1iwh: Difference between revisions
New page: left|200px<br /> <applet load="1iwh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iwh, resolution 1.55Å" /> '''Crystal Structure o... |
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[[Image:1iwh.gif|left|200px]]<br /> | [[Image:1iwh.gif|left|200px]]<br /><applet load="1iwh" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1iwh, resolution 1.55Å" /> | caption="1iwh, resolution 1.55Å" /> | ||
'''Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin'''<br /> | '''Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin'''<br /> | ||
==Overview== | ==Overview== | ||
Bezafibrate, an antilipidemic drug, is known as a potent allosteric | Bezafibrate, 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. | ||
==About this Structure== | ==About this Structure== | ||
1IWH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with HEM, CMO and PEM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1IWH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=CMO:'>CMO</scene> and <scene name='pdbligand=PEM:'>PEM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IWH OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Miura, S.]] | [[Category: Miura, S.]] | ||
[[Category: Park, S | [[Category: Park, S Y.]] | ||
[[Category: Shibayama, N.]] | [[Category: Shibayama, N.]] | ||
[[Category: Tame, J | [[Category: Tame, J R.H.]] | ||
[[Category: Yonetani, T.]] | [[Category: Yonetani, T.]] | ||
[[Category: CMO]] | [[Category: CMO]] | ||
| Line 27: | Line 26: | ||
[[Category: ligand-bezafibrate]] | [[Category: ligand-bezafibrate]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:16:22 2008'' | ||
Revision as of 14:16, 21 February 2008
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Crystal Structure of Horse Carbonmonoxyhemoglobin-Bezafibrate Complex at 1.55A Resolution: A Novel Allosteric Binding Site in R-State Hemoglobin
OverviewOverview
Bezafibrate, 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.
About this StructureAbout this Structure
1IWH is a Protein complex structure of sequences from Equus caballus with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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
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