PDBsum entry 2zmj

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protein ligands Protein-protein interface(s) links
Transcription PDB id
Protein chains
240 a.a. *
11 a.a. *
Waters ×16
* Residue conservation analysis
PDB id:
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
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
19-Apr-08     Release date:   02-Sep-08    
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Protein chain
Pfam   ArchSchema ?
P13053  (VDR_RAT) -  Vitamin D3 receptor
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.
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
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