2hb7: Difference between revisions
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|PDB= 2hb7 |SIZE=350|CAPTION= <scene name='initialview01'>2hb7</scene>, resolution 1.80Å | |PDB= 2hb7 |SIZE=350|CAPTION= <scene name='initialview01'>2hb7</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=O1C:2ALPHA-(3-HYDROXYPROPYL)-1ALPHA,25-DIHYDROXYVITAMIN D3'>O1C</scene> | |LIGAND= <scene name='pdbligand=O1C:2ALPHA-(3-HYDROXYPROPYL)-1ALPHA,25-DIHYDROXYVITAMIN+D3'>O1C</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1db1|1DB1]], [[1s0z|1S0Z]], [[1s19|1S19]], [[1ie8|1IE8]], [[1ie9|1IE9]], [[2ham|2HAM]], [[2har|2HAR]], [[2has|2HAS]], [[2hb8|2HB8]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hb7 OCA], [http://www.ebi.ac.uk/pdbsum/2hb7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hb7 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures. | The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
[[Category: Rochel, N.]] | [[Category: Rochel, N.]] | ||
[[Category: alpha helical sandwich]] | [[Category: alpha helical sandwich]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:28:00 2008'' | ||
Revision as of 03:28, 31 March 2008
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| , resolution 1.80Å | |||||||
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| Ligands: | |||||||
| Related: | 1DB1, 1S0Z, 1S19, 1IE8, 1IE9, 2HAM, 2HAR, 2HAS, 2HB8
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of VDR LBD in complex with 2alpha(3-hydroxy-1-propyl) calcitriol
OverviewOverview
The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures.
About this StructureAbout this Structure
2HB7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues., Hourai S, Fujishima T, Kittaka A, Suhara Y, Takayama H, Rochel N, Moras D, J Med Chem. 2006 Aug 24;49(17):5199-205. PMID:16913708
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