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PDBsum entry 2ayr

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Transcription PDB id
2ayr
Jmol
Contents
Protein chain
246 a.a. *
Ligands
L4G
Waters ×117
* Residue conservation analysis
PDB id:
2ayr
Name: Transcription
Title: A serm designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats
Structure: Estrogen receptor. Chain: a. Fragment: ligand binding domain, residues 304-551. Synonym: er, estradiol receptor, er-alpha. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: esr1, esr, nr3a1. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.229     R-free:   0.263
Authors: C.W.Hummel,A.G.Geiser,H.U.Bryant,I.R.Cohen,R.D.Dally, K.C.Fong,S.A.Frank,R.Hinklin,S.A.Jones,G.Lewis,D.J.Mccann, T.A.Shepherd,H.Tian,D.G.Rudman,O.B.Wallace,Y.Wang,J.A.Dodge
Key ref: C.W.Hummel et al. (2005). A selective estrogen receptor modulator designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats. J Med Chem, 48, 6772-6775. PubMed id: 16250633 DOI: 10.1021/jm050723z
Date:
07-Sep-05     Release date:   22-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03372  (ESR1_HUMAN) -  Estrogen receptor
Seq:
Struc:
 
Seq:
Struc:
595 a.a.
246 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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     3 terms  

 

 
DOI no: 10.1021/jm050723z J Med Chem 48:6772-6775 (2005)
PubMed id: 16250633  
 
 
A selective estrogen receptor modulator designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats.
C.W.Hummel, A.G.Geiser, H.U.Bryant, I.R.Cohen, R.D.Dally, K.C.Fong, S.A.Frank, R.Hinklin, S.A.Jones, G.Lewis, D.J.McCann, D.G.Rudmann, T.A.Shepherd, H.Tian, O.B.Wallace, M.Wang, Y.Wang, J.A.Dodge.
 
  ABSTRACT  
 
The design of a novel selective estrogen receptor modulator (SERM) for the potential treatment of uterine leiomyoma is described. 16 (LY2066948-HCl) binds with high affinity to estrogen receptors alpha and beta (ERalpha and ERbeta, respectively) and is a potent uterine antagonist with minimal effects on the ovaries as determined by serum biomarkers and histologic evaluation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20055500 C.H.Cho, B.Neuenswander, and R.C.Larock (2010).
Diverse methyl sulfone-containing benzo[b]thiophene library via iodocyclization and palladium-catalyzed coupling.
  J Comb Chem, 12, 278-285.  
19063592 A.Amadasi, A.Mozzarelli, C.Meda, A.Maggi, and P.Cozzini (2009).
Identification of xenoestrogens in food additives by an integrated in silico and in vitro approach.
  Chem Res Toxicol, 22, 52-63.  
19152365 F.Fontaine, S.Cross, G.Plasencia, M.Pastor, and I.Zamora (2009).
SHOP: a method for structure-based fragment and scaffold hopping.
  ChemMedChem, 4, 427-439.  
  19293997 J.P.Salisbury, and J.C.Williams (2009).
Docking study of triphenylphosphonium cations as estrogen receptor alpha modulators.
  Bioinformation, 3, 303-307.  
18936111 Z.Qin, I.Kastrati, R.T.Ashgodom, D.D.Lantvit, C.R.Overk, Y.Choi, R.B.van Breemen, J.L.Bolton, and G.R.Thatcher (2009).
Structural modulation of oxidative metabolism in design of improved benzothiophene selective estrogen receptor modulators.
  Drug Metab Dispos, 37, 161-169.  
17630709 H.Liu, Z.Qin, G.R.Thatcher, and J.L.Bolton (2007).
Uterine peroxidase-catalyzed formation of diquinone methides from the selective estrogen receptor modulators raloxifene and desmethylated arzoxifene.
  Chem Res Toxicol, 20, 1676-1684.  
16914190 P.Ascenzi, A.Bocedi, and M.Marino (2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
  Mol Aspects Med, 27, 299-402.  
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.