4M8H: Crystal Structure Of Human Retinoid X Receptor Alpha-ligand Binding Domain Complex With (r)4-methyl 9cuab30 And Coactivator Peptide Grip- 1

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid, 9cUAB30, is a selective rexinoid for the retinoid X nuclear receptors (RXR). 9cUAB30 displays substantial chemopreventive capacity with little toxicity and is being translated to the clinic as a novel cancer prevention agent. To improve on the potency of 9cUAB30, we synthesized 4-methyl analogs of 9cUAB30, which introduced chirality at the 4-position of the tetralone ring. The syntheses and biological evaluations of the racemic homolog and enantiomers are reported. We demonstrate that the S-enantiomer is the most potent and least toxic even though these enantiomers bind in a similar conformation in the ligand binding domain of RXR.
PDB ID: 4M8HDownload
MMDB ID: 116856
PDB Deposition Date: 2013/8/13
Updated in MMDB: 2014/01
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4M8H: dimeric; determined by author and by software (PISA)
Molecular Components in 4M8H
Label Count Molecule
Proteins (2 molecules)
Retinoic Acid Receptor Rxr-alpha(Gene symbol: RXRA)
Molecule annotation
Nuclear Receptor Coactivator 2(Gene symbol: NCOA2)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

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