5zwe: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Covalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having a vinyl ketone group via conjugate addition reaction== | |||
<StructureSection load='5zwe' size='340' side='right' caption='[[5zwe]], [[Resolution|resolution]] 2.72Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5zwe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZWE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZWE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9K0:(6R)-6-[(1R,3aS,4E,7aR)-7a-methyl-4-[2-[(3R,5R)-4-methylidene-3,5-bis(oxidanyl)cyclohexylidene]ethylidene]-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]hept-1-en-3-one'>9K0</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zwe OCA], [http://pdbe.org/5zwe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zwe RCSB], [http://www.ebi.ac.uk/pdbsum/5zwe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zwe ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:17227670</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We designed and synthesized vitamin D analogues with an electrophile as covalent modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an electrophilic enone group at the side chain for conjugate addition to His301 or His393 in the VDR. All compounds showed specific VDR-binding potency and agonistic activity. Covalent bond formations of 1-4 with the ligand-binding domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry. All compounds were shown to covalently bind to the VDR-LBD, and the abundance of VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time. Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301 in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent bond with VDR-LBD. | |||
Identification of the Histidine Residue in Vitamin D Receptor That Covalently Binds to Electrophilic Ligands.,Yoshizawa M, Itoh T, Hori T, Kato A, Anami Y, Yoshimoto N, Yamamoto K J Med Chem. 2018 Jul 11. doi: 10.1021/acs.jmedchem.8b00774. PMID:29936834<ref>PMID:29936834</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 5zwe" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Anami, Y]] | |||
[[Category: Itoh, T]] | [[Category: Itoh, T]] | ||
[[Category: Kato, A]] | [[Category: Kato, A]] | ||
[[Category: Yamamoto, K]] | |||
[[Category: Yoshimoto, N]] | [[Category: Yoshimoto, N]] | ||
[[Category: Yoshizawa, M]] | [[Category: Yoshizawa, M]] | ||
[[Category: Hormone covalent modifier transcription factor vitamind3 enone michael addition electrophile]] | |||
[[Category: Transcription]] | |||
Revision as of 10:33, 18 July 2018
Covalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having a vinyl ketone group via conjugate addition reactionCovalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having a vinyl ketone group via conjugate addition reaction
Structural highlights
Function[VDR_RAT] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.[1] Publication Abstract from PubMedWe designed and synthesized vitamin D analogues with an electrophile as covalent modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an electrophilic enone group at the side chain for conjugate addition to His301 or His393 in the VDR. All compounds showed specific VDR-binding potency and agonistic activity. Covalent bond formations of 1-4 with the ligand-binding domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry. All compounds were shown to covalently bind to the VDR-LBD, and the abundance of VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time. Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301 in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent bond with VDR-LBD. Identification of the Histidine Residue in Vitamin D Receptor That Covalently Binds to Electrophilic Ligands.,Yoshizawa M, Itoh T, Hori T, Kato A, Anami Y, Yoshimoto N, Yamamoto K J Med Chem. 2018 Jul 11. doi: 10.1021/acs.jmedchem.8b00774. PMID:29936834[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||