TY - JOUR
T1 - Interaction between vitamin D receptor and vitamin D ligands
T2 - Two-dimensional alanine scanning mutational analysis
AU - Choi, Mihwa
AU - Yamamoto, Keiko
AU - Itoh, Toshimasa
AU - Makishima, Makoto
AU - Mangelsdorf, David J.
AU - Moras, Dino
AU - DeLuca, Hector F.
AU - Yamada, Sachiko
PY - 2003/3/1
Y1 - 2003/3/1
N2 - We present a new method to investigate the details of interaction between vitamin D nuclear receptor (VDR) and various ligands, namely a two-dimensional alanine scanning mutational analysis. In this method, the transactivation of various ligands is studied in conjunction with a series of alanine scanning mutations of the residues lining the ligand binding pocket (LBP) of VDR, and the complete set of results is profiled in a patch table. We investigated examples from four structurally diverse groups of known VDR ligands: the native vitamin D hormone and two compounds with the same side chain configuration; four 20-epi compounds; three 19-nor compounds; and two nonsecosteroids. The patch table of the results indicates characteristics of each group in terms of its interaction with 18 LBP residues. We demonstrate the validity of this approach by application to docking studies of the two nonsecosteroids.
AB - We present a new method to investigate the details of interaction between vitamin D nuclear receptor (VDR) and various ligands, namely a two-dimensional alanine scanning mutational analysis. In this method, the transactivation of various ligands is studied in conjunction with a series of alanine scanning mutations of the residues lining the ligand binding pocket (LBP) of VDR, and the complete set of results is profiled in a patch table. We investigated examples from four structurally diverse groups of known VDR ligands: the native vitamin D hormone and two compounds with the same side chain configuration; four 20-epi compounds; three 19-nor compounds; and two nonsecosteroids. The patch table of the results indicates characteristics of each group in terms of its interaction with 18 LBP residues. We demonstrate the validity of this approach by application to docking studies of the two nonsecosteroids.
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U2 - 10.1016/S1074-5521(03)00050-4
DO - 10.1016/S1074-5521(03)00050-4
M3 - Article
C2 - 12670540
AN - SCOPUS:0037351986
SN - 1074-5521
VL - 10
SP - 261
EP - 270
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 3
ER -