spacer
spacer

PDBsum entry 2zmj

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transcription PDB id
2zmj
Jmol
Contents
Protein chains
240 a.a. *
11 a.a. *
Ligands
MI4
Waters ×16
* Residue conservation analysis
PDB id:
2zmj
Name: Transcription
Title: Crystal structure of rat vitamin d receptor bound to adamantyl vitamin d analogs: structural basis for vitamin d receptor antagonism and/or partial agonism
Structure: Vitamin d3 receptor. Chain: a. Fragment: ligand binding domain, unp residues 116-423. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor, nuclear receptor subfamily 1 group i member 1. Engineered: yes. Mutation: yes. Mediator of RNA polymerase ii transcription subunit 1.
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: vdr, nr1i1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide
Resolution:
2.35Å     R-factor:   0.222     R-free:   0.271
Authors: M.Nakabayashi,S.Yamada,T.Tanaka,M.Igarashi,N.Yoshimoto, T.Ikura,N.Ito,M.Makishima,H.Tokiwa,H.F.Deluca,M.Shimizu
Key ref: M.Nakabayashi et al. (2008). Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D analogs: structural basis for vitamin D receptor antagonism and partial agonism. J Med Chem, 51, 5320-5329. PubMed id: 18710208 DOI: 10.1021/jm8004477
Date:
19-Apr-08     Release date:   02-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13053  (VDR_RAT) -  Vitamin D3 receptor
Seq:
Struc:
423 a.a.
240 a.a.
Protein chain
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  

 

 
DOI no: 10.1021/jm8004477 J Med Chem 51:5320-5329 (2008)
PubMed id: 18710208  
 
 
Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D analogs: structural basis for vitamin D receptor antagonism and partial agonism.
M.Nakabayashi, S.Yamada, N.Yoshimoto, T.Tanaka, M.Igarashi, T.Ikura, N.Ito, M.Makishima, H.Tokiwa, H.F.DeLuca, M.Shimizu.
 
  ABSTRACT  
 
The X-ray crystal structures of the rat VDR ligand-binding domain complexed with 19-norvitamin D compounds that contain an adamantyl substituent at the side-chain terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) and a coactivator peptide derived from DRIP205 are reported. These compounds show a series of partial agonistic (10-75% efficacy)/antagonistic activities. All of these complexed receptors are crystallized in the canonical active conformation, regardless of their activity profiles. The bulky adamantyl side chain does not crowd helix 12 but protrudes into the gap formed by helix 11, loop 11-12, helix 3, and loop 6-7, thereby widening the ligand binding pocket. We suggest that these structural changes destabilize the active protein conformation and reduce its contribution to equilibrium among the active and inactive conformations. The coactivator peptide traps the minor active conformation, and the equilibrium shifts to the active conformation. As a result, these ligands show partial agonistic activities.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354674 J.Liu, D.Obando, V.Liao, T.Lifa, and R.Codd (2011).
The many faces of the adamantyl group in drug design.
  Eur J Med Chem, 46, 1949-1963.  
19372222 H.C.Raaijmakers, J.E.Versteegh, and J.C.Uitdehaag (2009).
The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation.
  J Biol Chem, 284, 19572-19579.
PDB code: 2w8y
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.