PMID- 15326291
OWN - NLM
STAT- MEDLINE
DCOM- 20041116
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 35
DP  - 2004 Aug 31
TI  - Identification of an alternative ligand-binding pocket in the nuclear vitamin D 
      receptor and its functional importance in 1alpha,25(OH)2-vitamin D3 signaling.
PG  - 12876-81
AB  - Structural and molecular studies have shown that the vitamin D receptor (VDR) 
      mediates 1alpha,25(OH)2-vitamin D3 gene transactivation. Recent evidence 
      indicates that both VDR and the estrogen receptor are localized to plasma 
      membrane caveolae and are required for initiation of nongenomic (NG) responses. 
      Computer docking of the NG-specific 1alpha,25(OH)2-lumisterol to the VDR resulted 
      in identification of an alternative ligand-binding pocket that partially overlaps 
      the genomic pocket described in the experimentally determined x-ray structure. 
      Data obtained from docking five different vitamin D sterols in the genomic and 
      alternative pockets were used to generate a receptor conformational ensemble 
      model, providing an explanation for how VDR and possibly the estrogen receptor 
      can have genomic and NG functionality. The VDR model is compatible with the 
      following: (i) NG chloride channel agonism and antagonism; (ii) variable 
      ligand-stabilized trypsin digest banding patterns; and (iii) differential 
      transcriptional activity, employing different VDR point mutants and 
      1alpha,25(OH)2-vitamin D3 analogs.
CI  - Copyright 2004 The National Academy of Sciencs of the USA
FAU - Mizwicki, Mathew T
AU  - Mizwicki MT
AD  - Department of Biochemistry, University of California, Riverside, CA 92521, USA.
FAU - Keidel, Don
AU  - Keidel D
FAU - Bula, Craig M
AU  - Bula CM
FAU - Bishop, June E
AU  - Bishop JE
FAU - Zanello, Laura P
AU  - Zanello LP
FAU - Wurtz, Jean-Marie
AU  - Wurtz JM
FAU - Moras, Dino
AU  - Moras D
FAU - Norman, Anthony W
AU  - Norman AW
LA  - eng
GR  - F32 DK009012/DK/NIDDK NIH HHS/United States
GR  - R01 DK009012/DK/NIDDK NIH HHS/United States
GR  - DK-09012/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040823
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chloride Channels)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Binding Sites
MH  - Calcitriol/*metabolism
MH  - Cell Nucleus/*chemistry/metabolism
MH  - Chloride Channels/metabolism
MH  - Ligands
MH  - Models, Molecular
MH  - Point Mutation
MH  - Protein Conformation
MH  - Receptors, Calcitriol/*chemistry/genetics/metabolism
MH  - Signal Transduction/*physiology
PMC - PMC516488
EDAT- 2004/08/25 05:00
MHDA- 2004/11/17 09:00
PMCR- 2005/02/28
CRDT- 2004/08/25 05:00
PHST- 2004/08/25 05:00 [pubmed]
PHST- 2004/11/17 09:00 [medline]
PHST- 2004/08/25 05:00 [entrez]
PHST- 2005/02/28 00:00 [pmc-release]
AID - 0403606101 [pii]
AID - 10112876 [pii]
AID - 10.1073/pnas.0403606101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12876-81. doi: 
      10.1073/pnas.0403606101. Epub 2004 Aug 23.