2har
From Proteopedia
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|PDB= 2har |SIZE=350|CAPTION= <scene name='initialview01'>2har</scene>, resolution 1.90Å | |PDB= 2har |SIZE=350|CAPTION= <scene name='initialview01'>2har</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=OCC:2ALPHA-(3-HYDROXYPROPOXY)-1ALPHA,25-DIHYDROXYVITAMIN D3'>OCC</scene> | + | |LIGAND= <scene name='pdbligand=OCC:2ALPHA-(3-HYDROXYPROPOXY)-1ALPHA,25-DIHYDROXYVITAMIN+D3'>OCC</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1db1|1DB1]], [[1s19|1S19]], [[1s0z|1S0Z]], [[1txi|1TXI]], [[1ie8|1IE8]], [[1ie9|1IE9]], [[2ham|2HAM]], [[2has|2HAS]], [[2hb7|2HB7]], [[2hb8|2HB8]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2har OCA], [http://www.ebi.ac.uk/pdbsum/2har PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2har 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Osteoporosis, involutional, 166710 (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601769 601769]], Rickets, vitamin D-resistant, type IIA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601769 601769]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
[[Category: Rochel, N.]] | [[Category: Rochel, N.]] | ||
| - | [[Category: OCC]] | ||
[[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 03:27:49 2008'' |
Revision as of 00:27, 31 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Related: | 1DB1, 1S19, 1S0Z, 1TXI, 1IE8, 1IE9, 2HAM, 2HAS, 2HB7, 2HB8
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of VDR LBD in complex with 2 alpha-(3-hydroxy-1-propoxy) calcitriol
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.
About this Structure
2HAR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 03:27:49 2008
