1s0z: Difference between revisions

Latest revision as of 08:27, 14 February 2024

Crystal structure of the VDR LBD complexed to seocalcitol.

Structural highlights

1s0z is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	EB1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

VDR_HUMAN Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:277440. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Function

VDR_HUMAN 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.^[11] ^[12] ^[13] ^[14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O'Malley BW. Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science. 1988 Dec 23;242(4886):1702-5. PMID:2849209
↑ Yagi H, Ozono K, Miyake H, Nagashima K, Kuroume T, Pike JW. A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1993 Feb;76(2):509-12. PMID:8381803
↑ Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y. A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet. 1991 Sep;49(3):668-73. PMID:1652893
↑ Sone T, Marx SJ, Liberman UA, Pike JW. A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1990 Apr;4(4):623-31. PMID:2177843
↑ Malloy PJ, Weisman Y, Feldman D. Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain. J Clin Endocrinol Metab. 1994 Feb;78(2):313-6. PMID:8106618
↑ Kristjansson K, Rut AR, Hewison M, O'Riordan JL, Hughes MR. Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3. J Clin Invest. 1993 Jul;92(1):12-6. PMID:8392085 doi:https://dx.doi.org/10.1172/JCI116539
↑ Rut AR, Hewison M, Kristjansson K, Luisi B, Hughes MR, O'Riordan JL. Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures. Clin Endocrinol (Oxf). 1994 Nov;41(5):581-90. PMID:7828346
↑ Lin NU, Malloy PJ, Sakati N, al-Ashwal A, Feldman D. A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1996 Jul;81(7):2564-9. PMID:8675579
↑ Whitfield GK, Selznick SH, Haussler CA, Hsieh JC, Galligan MA, Jurutka PW, Thompson PD, Lee SM, Zerwekh JE, Haussler MR. Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner. Mol Endocrinol. 1996 Dec;10(12):1617-31. PMID:8961271
↑ Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest. 1997 Jan 15;99(2):297-304. PMID:9005998 doi:10.1172/JCI119158
↑ Fujiki R, Kim MS, Sasaki Y, Yoshimura K, Kitagawa H, Kato S. Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J. 2005 Nov 16;24(22):3881-94. Epub 2005 Oct 27. PMID:16252006 doi:10.1038/sj.emboj.7600853
↑ Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000 Jan;5(1):173-9. PMID:10678179
↑ Eelen G, Verlinden L, Rochel N, Claessens F, De Clercq P, Vandewalle M, Tocchini-Valentini G, Moras D, Bouillon R, Verstuyf A. Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D explained by vitamin D receptor-coactivator interaction. Mol Pharmacol. 2005 May;67(5):1566-73. Epub 2005 Feb 22. PMID:15728261 doi:10.1124/mol.104.008730
↑ Hourai S, Fujishima T, Kittaka A, Suhara Y, Takayama H, Rochel N, Moras D. Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues. J Med Chem. 2006 Aug 24;49(17):5199-205. PMID:16913708 doi:https://dx.doi.org/10.1021/jm0604070

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O'Malley BW. Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science. 1988 Dec 23;242(4886):1702-5. PMID:2849209

[2] Yagi H, Ozono K, Miyake H, Nagashima K, Kuroume T, Pike JW. A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1993 Feb;76(2):509-12. PMID:8381803

[3] Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y. A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet. 1991 Sep;49(3):668-73. PMID:1652893

[4] Sone T, Marx SJ, Liberman UA, Pike JW. A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1990 Apr;4(4):623-31. PMID:2177843

[5] Malloy PJ, Weisman Y, Feldman D. Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain. J Clin Endocrinol Metab. 1994 Feb;78(2):313-6. PMID:8106618

[6] Kristjansson K, Rut AR, Hewison M, O'Riordan JL, Hughes MR. Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3. J Clin Invest. 1993 Jul;92(1):12-6. PMID:8392085 doi:https://dx.doi.org/10.1172/JCI116539

[7] Rut AR, Hewison M, Kristjansson K, Luisi B, Hughes MR, O'Riordan JL. Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures. Clin Endocrinol (Oxf). 1994 Nov;41(5):581-90. PMID:7828346

[8] Lin NU, Malloy PJ, Sakati N, al-Ashwal A, Feldman D. A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1996 Jul;81(7):2564-9. PMID:8675579

[9] Whitfield GK, Selznick SH, Haussler CA, Hsieh JC, Galligan MA, Jurutka PW, Thompson PD, Lee SM, Zerwekh JE, Haussler MR. Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner. Mol Endocrinol. 1996 Dec;10(12):1617-31. PMID:8961271

[10] Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest. 1997 Jan 15;99(2):297-304. PMID:9005998 doi:10.1172/JCI119158

[11] Fujiki R, Kim MS, Sasaki Y, Yoshimura K, Kitagawa H, Kato S. Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J. 2005 Nov 16;24(22):3881-94. Epub 2005 Oct 27. PMID:16252006 doi:10.1038/sj.emboj.7600853

[12] Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000 Jan;5(1):173-9. PMID:10678179

[13] Eelen G, Verlinden L, Rochel N, Claessens F, De Clercq P, Vandewalle M, Tocchini-Valentini G, Moras D, Bouillon R, Verstuyf A. Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D explained by vitamin D receptor-coactivator interaction. Mol Pharmacol. 2005 May;67(5):1566-73. Epub 2005 Feb 22. PMID:15728261 doi:10.1124/mol.104.008730

[14] Hourai S, Fujishima T, Kittaka A, Suhara Y, Takayama H, Rochel N, Moras D. Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues. J Med Chem. 2006 Aug 24;49(17):5199-205. PMID:16913708 doi:https://dx.doi.org/10.1021/jm0604070

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@@ Line 3: / Line 3: @@
 <StructureSection load='1s0z' size='340' side='right'caption='[[1s0z]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1s0z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S0Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1S0Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1s0z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S0Z FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EB1:SEOCALCITOL'>EB1</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]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1db1|1db1]], [[1ie8|1ie8]], [[1ie9|1ie9]], [[1s19|1s19]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EB1:SEOCALCITOL'>EB1</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1s0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s0z OCA], [https://pdbe.org/1s0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s0z RCSB], [https://www.ebi.ac.uk/pdbsum/1s0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s0z ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1s0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s0z OCA], [http://pdbe.org/1s0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1s0z RCSB], [http://www.ebi.ac.uk/pdbsum/1s0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1s0z ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
+[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://omim.org/entry/277440 277440]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] 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:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
+[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] 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:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 23: / Line 22: @@
 </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=1s0z ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-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.
-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<ref>PMID:15055995</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 1s0z" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 40: / Line 30: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Moras, D]]
+[[Category: Moras D]]
-[[Category: Rochel, N]]
+[[Category: Rochel N]]
-[[Category: Tocchini-Valentini, G]]
+[[Category: Tocchini-Valentini G]]
-[[Category: Wurtz, J M]]
+[[Category: Wurtz JM]]
-[[Category: Alpha-helical sandwich]]
-[[Category: Gene regulation]]
-[[Category: Nuclear receptor]]
-[[Category: Transcription regulation]]

1s0z: Difference between revisions

Latest revision as of 08:27, 14 February 2024

Crystal structure of the VDR LBD complexed to seocalcitol.

Structural highlights

Disease

Function

Evolutionary Conservation

See Also

References

Contents

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