:
Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding
domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit
coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of
evidence report that selective long chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA),
docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to
transcriptional activation. We therefore hypothesize that selective PUFAs would modulate the dynamics and kinetics of
VDRs, irrespective bioactive of vitamin-D binding. The spatial arrangements of the selected PUFAs in VDR active site
were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific
binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared
to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR
(PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the
stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of
PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.
Cloning of the gene for poly(3-hydroxybutyric acid) depolymerase of Comamonas testosteroni and functional analysis of its substrate-binding domain