2ouz: Difference between revisions
New page: left|200px<br /> <applet load="2ouz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ouz, resolution 2.000Å" /> '''Crystal Structure ... |
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[[Image:2ouz.gif|left|200px]]<br /> | [[Image:2ouz.gif|left|200px]]<br /><applet load="2ouz" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2ouz, resolution 2.000Å" /> | caption="2ouz, resolution 2.000Å" /> | ||
'''Crystal Structure of Estrogen Receptor alpha-lasofoxifene complex'''<br /> | '''Crystal Structure of Estrogen Receptor alpha-lasofoxifene complex'''<br /> | ||
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==Overview== | ==Overview== | ||
Lasofoxifene is a new and potent selective estrogen receptor modulator, (SERM). The structural basis of its interaction with the estrogen receptor, has been investigated by crystallographic analysis of its complex with the, ligand-binding domain of estrogen receptor alpha at a resolution of 2.0 A., As with other SERMs, lasofoxifene diverts the receptor from its, agonist-bound conformation by displacing the C-terminal AF-2 helix into, the site at which the LXXLL motif of coactivator proteins would otherwise, be able to bind. Lasofoxifene achieves this effect by occupying the space, normally filled by residue Leu 540, as well as by modulating the, conformation of residues of helix 11 (His 524, Leu 525). A well-defined, salt bridge between lasofoxifene and Asp 351 suggests that charge, neutralization in this region of the receptor may explain the some of the, antiestrogenic effects of lasofoxifene. The results suggest general, features of ERalpha/SERM recognition, and add a new dimension to efforts, to rationalize differences between the biological activity profiles, exhibited by these important pharmacological agents. | Lasofoxifene is a new and potent selective estrogen receptor modulator, (SERM). The structural basis of its interaction with the estrogen receptor, has been investigated by crystallographic analysis of its complex with the, ligand-binding domain of estrogen receptor alpha at a resolution of 2.0 A., As with other SERMs, lasofoxifene diverts the receptor from its, agonist-bound conformation by displacing the C-terminal AF-2 helix into, the site at which the LXXLL motif of coactivator proteins would otherwise, be able to bind. Lasofoxifene achieves this effect by occupying the space, normally filled by residue Leu 540, as well as by modulating the, conformation of residues of helix 11 (His 524, Leu 525). A well-defined, salt bridge between lasofoxifene and Asp 351 suggests that charge, neutralization in this region of the receptor may explain the some of the, antiestrogenic effects of lasofoxifene. The results suggest general, features of ERalpha/SERM recognition, and add a new dimension to efforts, to rationalize differences between the biological activity profiles, exhibited by these important pharmacological agents. | ||
==About this Structure== | ==About this Structure== | ||
2OUZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with C3D as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2OUZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=C3D:'>C3D</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OUZ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: serm]] | [[Category: serm]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:21:36 2008'' | ||
