Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Ligand recognition by the vitamin D receptor
Autore:
Choi, MW; Yamamoto, K; Masuno, H; Nakashima, K; Taga, T; Yamada, S;
Indirizzi:
Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan Tokyo Med & Dent Univ Tokyo Japan 1010062 iyoda Ku, Tokyo 1010062, Japan Tokyo Med & Dent Univ, Med Res Inst, Chiyoda Ku, Tokyo 1010062, Japan Tokyo Med & Dent Univ Tokyo Japan 1010062 iyoda Ku, Tokyo 1010062, Japan
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 7, volume: 9, anno: 2001,
pagine: 1721 - 1730
SICI:
0968-0896(200107)9:7<1721:LRBTVD>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
THYROID-HORMONE RECEPTOR; SIDE-CHAIN CONFORMATION; D-RESISTANT RICKETS; NUCLEAR RECEPTOR; BINDING DOMAIN; CRYSTAL-STRUCTURE; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; COACTIVATOR INTERACTIONS; 3-DIMENSIONAL STRUCTURE; RETINOIC ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Yamamoto, K Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, 2-3-10 SurugadaiKanda, Tokyo 1010062, Japan Tokyo Med & Dent Univ 2-3-10 Surugadai Kanda Tokyo Japan 1010062
Citazione:
M.W. Choi et al., "Ligand recognition by the vitamin D receptor", BIO MED CH, 9(7), 2001, pp. 1721-1730

Abstract

Three-dimensional structure of the ligand binding domain (LBD) of the vitamin D receptor (VDR) docked with the natural ligand 1 alpha ,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] has been mostly solved by the X-ray crystallographic analysis of the deletion mutant (VDR-LBD Delta 165-215). The important focus, from now on. is how the VDR recognizes and interacts with potent synthetic ligands. We now report the docking models of the VDR with three functionally and structurally interesting ligands, 22-oxa-1.25-(OH)(2)D-3 (OCT), 20-epi-1,25-(OH)(2)D-3 and 20-epi-22-oxa-24,26,27-trihomo-1.25-(OH)(2)D-3. In parallel with the computational docking studies, we prepared twelve one-point mutants of amino acid residues lining the ligand binding pocket of the VDR and examined their transactivation potency induced by 1125-(OH)(2)D-3 and these synthetic ligands. The results indicate that L233, R274, W286, H397 and Y401 are essential for holding the all ligands tested, S278 andQ400 are not important at all, and the importance of S237, V234, S275, C288 and H305 is variable depending on the side-chain structure of the ligands. Based on these studies, we suggested key structural factors to bestow theselective action on OCT and the augmented activities on 20-epi-ligands. Furthermore, the docking models coincided well with our proposed active space-region theory of vitamin D based on the conformational analyses of ligands. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 01:24:40