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Figure 1.
Fig. 1. (A) Structure of the LBD of the human xenobiotic
receptor PXR. Residues 142 to 177 and 198 to 431 of hPXR in
complex with three orientations of SR12813 are shown;  helices
are in red and  strands
are in green, including the two novel strands,
1 and 1' that
complete the five-stranded antiparallel sheet
observed in this structure. Secondary structural elements are
numbered according to the RXR structure (19). See also Web fig.
1 (25). (B) hPXR-LDB electron density: unbiased (F[obs]  F[calc])
electron density into which the novel 1/ 1' strands
(residues 210 to 228) of hPXR were traced (2.75 Å
resolution, contoured at 1.2  ). (C and
D) The ligand-binding cavity of hPXR. A cutaway view of the
binding cavity, including electrostatic surface potentials
(positive in blue, negative in red), reveals a relatively
smooth, uncharged surface. The cavity is enclosed by portions of
five helices (
3, 5, 7, 10, and
AF), three
strands (
1, 3, and 4), and
three loops (the 10- AF region
and the two mobile regions between 4 and 7 and from
residue 198 to 1). Select
residues lining the cavity are indicated. In particular, the
positions of the following polar residues that contact SR12813
are indicated in red: Ser208, Ser247, Gln285, His407, and
Arg410. Regions of the surface 309-321 loop, which may
facilitate the expansion of the ligand-binding pocket, are also
shown, including the conserved hydrophobic residues Phe^315,
Leu318, Leu319, and Leu320.
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