Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

2ZFX

Crystal structure of the rat vitamin D receptor ligand binding domain complexed with YR301 and a synthetic peptide containing the NR2 box of DRIP 205

Summary for 2ZFX
Entry DOI10.2210/pdb2zfx/pdb
DescriptorVitamin D3 receptor, DRIP 205 NR2 box peptide, (2S)-3-{4-[1-ethyl-1-(4-{[(2R)-2-hydroxy-3,3-dimethylbutyl]oxy}-3-methylphenyl)propyl]-2-methylphenoxy}propane-1,2-diol, ... (4 entities in total)
Functional Keywordshormone/growth factor receptor, dna-binding, metal-binding, nucleus, phosphoprotein, transcription, transcription regulation, zinc, zinc-finger, activator, alternative splicing, polymorphism
Biological sourceRattus norvegicus (rat)
More
Cellular locationNucleus: P13053 Q15648
Total number of polymer chains2
Total formula weight32085.03
Authors
Kakuda, S.,Takimoto-Kamimura, M. (deposition date: 2008-01-15, release date: 2009-01-20, Last modification date: 2024-03-13)
Primary citationKakuda, S.,Okada, K.,Eguchi, H.,Takenouchi, K.,Hakamata, W.,Kurihara, M.,Takimoto-Kamimura, M.
Structure of the ligand-binding domain of rat VDR in complex with the nonsecosteroidal vitamin D3 analogue YR301
Acta Crystallogr.,Sect.F, 64:970-973, 2008
Cited by
PubMed Abstract: Vitamin D receptor (VDR) is a ligand-inducible hormone receptor that mediates 1alpha,25(OH)(2)D(3) action, regulating calcium and phosphate metabolism, induces potent cell differentiation activity and has immunosuppressive effects. Analogues of 1alpha,25(OH)(2)D(3) have been used clinically for some years. However, the risk of potential side effects limits the use of these substances. LG190178 is a novel nonsecosteroidal ligand for VDR. (2S)-3-[4-(3-{4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl}pentan-3-yl)-2-methylphenoxy] propane-1,2-diol (YR301) is the only one of the four evaluated stereoisomers of LG190178 to have strong activity. To understand the strong activity of YR301, the crystal structure of YR301 complexed with the rat VDR ligand-binding domain (VDR LBD) was solved at 2.0 A resolution and compared with the structure of the VDR LBD-1alpha,25(OH)(2)D(3) complex. YR301 and 1alpha,25(OH)(2)D(3) share the same position and the diethylmethyl group occupies a similar space to the C and D rings of 1alpha,25(OH)(2)D(3). YR301 has two characteristic hydroxyl groups which contribute to its potent activity. The first is 2'-OH, which forms hydrogen bonds to the NE2 atoms of both His301 and His393. The other is 2-OH, which interacts with Ser233 OG and Arg270 NH1. These two hydroxyl groups of YR301 correspond exactly to 25-OH and 1-OH, respectively, of 1alpha,25(OH)(2)D(3). The terminal hydroxyl group (3-OH) of YR301 is directly hydrogen bonded to Arg270 and also interacts indirectly with Tyr232 OH and the backbone NH of Asp144 via water molecules. Additional derivatization of the terminal hydroxyl group using the positions of the water molecules might be useful for the design of more potent compounds.
PubMed: 18997319
DOI: 10.1107/S1744309108026754
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.99 Å)
Structure validation

239492

数据于2025-07-30公开中

PDB statisticsPDBj update infoContact PDBjnumon