1s19
From Proteopedia
(New page: 200px<br /> <applet load="1s19" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s19, resolution 2.1Å" /> '''Crystal structure of...) |
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| - | [[Image:1s19.gif|left|200px]]<br /> | + | [[Image:1s19.gif|left|200px]]<br /><applet load="1s19" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1s19" size=" | + | |
caption="1s19, resolution 2.1Å" /> | caption="1s19, resolution 2.1Å" /> | ||
'''Crystal structure of VDR ligand binding domain complexed to calcipotriol.'''<br /> | '''Crystal structure of VDR ligand binding domain complexed to calcipotriol.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The plethora of actions of 1alpha,25(OH)(2)D(3) in various systems | + | The plethora of actions of 1alpha,25(OH)(2)D(3) in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of these ligands. Here, we report the crystal structures of VDR ligand binding domain bound to two vitamin D agonists of therapeutical interest, calcipotriol and seocalcitol, which are characterized by their side chain modifications. These structures show the conservation of the VDR structure and the adaptation of the side chain anchored by hydroxyl moieties. The structure of VDR-calcipotriol helps us to understand the structural basis for for the switching of calcipotriol to a receptor antagonist by further side chain modification. The VDR-seocalcitol structure, in comparison with the structure of VDR-KH1060, a superagonist ligand closely related to seocalcitol, shows adaptation of the D ring and position of C-21 in order to adapt its more rigid side chain. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1S19 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 MC9 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1S19 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=MC9:'>MC9</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S19 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rochel, N.]] | [[Category: Rochel, N.]] | ||
[[Category: Tocchini-Valentini, G.]] | [[Category: Tocchini-Valentini, G.]] | ||
| - | [[Category: Wurtz, J | + | [[Category: Wurtz, J M.]] |
[[Category: MC9]] | [[Category: MC9]] | ||
[[Category: alpha-helical sandwich]] | [[Category: alpha-helical sandwich]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:56:49 2008'' |
Revision as of 12:56, 21 February 2008
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Crystal structure of VDR ligand binding domain complexed to calcipotriol.
Contents |
Overview
The plethora of actions of 1alpha,25(OH)(2)D(3) in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of these ligands. Here, we report the crystal structures of VDR ligand binding domain bound to two vitamin D agonists of therapeutical interest, calcipotriol and seocalcitol, which are characterized by their side chain modifications. These structures show the conservation of the VDR structure and the adaptation of the side chain anchored by hydroxyl moieties. The structure of VDR-calcipotriol helps us to understand the structural basis for for the switching of calcipotriol to a receptor antagonist by further side chain modification. The VDR-seocalcitol structure, in comparison with the structure of VDR-KH1060, a superagonist ligand closely related to seocalcitol, shows adaptation of the D ring and position of C-21 in order to adapt its more rigid side chain.
Disease
Known diseases associated with this structure: Osteoporosis, involutional, 166710 (1) OMIM:[601769], Rickets, vitamin D-resistant, type IIA OMIM:[601769]
About this Structure
1S19 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification., Tocchini-Valentini G, Rochel N, Wurtz JM, Moras D, J Med Chem. 2004 Apr 8;47(8):1956-61. PMID:15055995
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