Interaction between vitamin D receptor and vitamin D ligands: Two-dimensional alanine scanning mutational analysis

Mihwa Choi, Keiko Yamamoto, Toshimasa Itoh, Makoto Makishima, David J. Mangelsdorf, Dino Moras, Hector F. DeLuca, Sachiko Yamada

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalChemistry and Biology
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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