 |
PDBsum entry 4g20
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription/transcription inhibitor
|
PDB id
|
|
|
|
4g20
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transcription/transcription inhibitor
|
|
|
Title:
|
|
Structural basis for the accommodation of bis- and tris-aromatic derivatives in vitamin d nuclear receptor
|
|
Structure:
|
|
Vitamin d3 receptor a. Chain: a. Fragment: unp residues 156-453. Synonym: vdr-a, 1,25-dihydroxyvitamin d3 receptor a, nuclear receptor subfamily 1 group i member 1-a. Engineered: yes. Nuclear receptor coactivator 1. Chain: b. Fragment: unp residues 686-700.
|
|
Source:
|
|
Danio rerio. Leopard danio,zebra danio,zebra fish. Organism_taxid: 7955. Gene: vdra, nr1i1a, vdr. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Human.
|
|
Resolution:
|
|
|
2.90Å
|
R-factor:
|
0.233
|
R-free:
|
0.287
|
|
|
Authors:
|
|
F.Ciesielski,Y.Sato,D.Moras,N.Rochel
|
|
Key ref:
|
|
F.Ciesielski
et al.
(2012).
Structural basis for the accommodation of bis- and tris-aromatic derivatives in vitamin D nuclear receptor.
J Med Chem,
55,
8440-8449.
PubMed id:
|
|
|
Date:
|
|
|
11-Jul-12
|
Release date:
|
26-Sep-12
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q9PTN2
(VDRA_DANRE) -
Vitamin D3 receptor A from Danio rerio
|
|
|
|
Seq:
Struc:
|
|
|
|
453 a.a.
237 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
J Med Chem
55:8440-8449
(2012)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural basis for the accommodation of bis- and tris-aromatic derivatives in vitamin D nuclear receptor.
|
|
F.Ciesielski,
Y.Sato,
Y.Chebaro,
D.Moras,
A.Dejaegere,
N.Rochel.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Actual use of the active form of vitamin D (calcitriol or
1α,25-dihydroxyvitamin D(3)) to treat hyperproliferative disorders is hampered
by calcemic effects, hence the continuous development of chemically modified
analogues with dissociated profiles. Structurally distinct nonsecosteroidal
analogues have been developed to mimic calcitriol activity profiles with low
calcium serum levels. Here, we report the crystallographic study of vitamin D
nuclear receptor (VDR) ligand binding domain in complexes with six
nonsecosteroidal analogues harboring two or three phenyl rings. These compounds
induce a stimulated transcription in the nanomolar range, similar to calcitriol.
Examination of the protein-ligand interactions reveals the mode of binding of
these nonsecosteroidal compounds and highlights the role of the various chemical
modifications of the ligands to VDR binding and activity, notably (de)solvation
effects. The structures with the tris-aromatic ligands exhibit a rearrangement
of a novel region of the VDR ligand binding pocket, helix H6.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
