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Figure 5 | Nuclear Receptor

Figure 5

From: Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors)

Figure 5

Sequence alignment of the LBD of PXR, VDR, and CAR genes. The locations of the α-helices above the amino acid sequences are based on the structures determined from x-ray crystallography of human PXR and human VDR [73, 88]. Amino acid resides highlighted in bold type are residues in human PXR, human VDR, mouse CAR, and human CAR shown to directly interact with structurally diverse ligands. These residues have been determined by x-ray crystallography and, in some cases, by additional molecular modelling for human VDR [39, 88-90], rat VDR [91], human PXR [37, 38, 73], mouse CAR [40, 92], and human CAR [81]. The ligands for the various receptors are: human VDR – calcitriol [39, 88, 89], 20-epi calcitriol analogs [89], calcipotriol, seocalcitol [39], 1α,25-lumisterol [90]; rat VDR – 2-carbon substituted vitamin D3 analogs [91]; human PXR – SR12813 [73], hyperforin [38], rifampicin [37]; mouse CAR – 5α-androst-16-en-3α-ol (androstenol) [92], TCPOBOP [40]; and human CAR – 5β-pregnan-3,20-dione and 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO) [81]. The amino acid residues highlighted in red underlined boldin Xenopus laevis BXRα and BXRβ correspond to codons that show evidence of positive selection in a previously published phylogenetic analysis of nucleotide variation in the BXRα and/or BXRβ lineages [30]. Note that of the 23 amino acid residue positions identified as having high probability of having experienced positive selection in the BXRα and/or BXRβ lineages, 9 are orthologous to or adjacent to residues that are orthologous to human PXR residues shown to directly interact with the ligands SR12813, hyperforin, and/or rifampicin in x-ray crystallographic structures of the human PXR [37, 38, 73]; an additional two residues are orthologous to ligand-binding residues in human VDR [39, 88-90] and, also in one case, human and mouse CAR as well [40, 81, 92].

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