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PDBsum entry 2zvt

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protein ligands Protein-protein interface(s) links
Transcription PDB id
2zvt
Jmol
Contents
Protein chain
274 a.a. *
Ligands
PTG ×2
Waters ×184
* Residue conservation analysis
PDB id:
2zvt
Name: Transcription
Title: Cys285ser mutant ppargamma ligand-binding domain complexed with 15-deoxy-delta12,14-prostaglandin j2
Structure: Peroxisome proliferator-activated receptor gamma. Chain: a, b. Fragment: ligand-binding domain. Synonym: ppar-gamma, nuclear receptor subfamily 1 group c member 3. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pparg. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.90Å     R-factor:   0.251     R-free:   0.275
Authors: T.Waku,T.Oyama,T.Shiraki,K.Morikawa
Key ref: T.Waku et al. (2009). Atomic structure of mutant PPARgamma LBD complexed with 15d-PGJ2: novel modulation mechanism of PPARgamma/RXRalpha function by covalently bound ligands. FEBS Lett, 583, 320-324. PubMed id: 19101554 DOI: 10.1016/j.febslet.2008.12.017
Date:
19-Nov-08     Release date:   06-Oct-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
Seq:
Struc:
505 a.a.
274 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: 10.1016/j.febslet.2008.12.017 FEBS Lett 583:320-324 (2009)
PubMed id: 19101554  
 
 
Atomic structure of mutant PPARgamma LBD complexed with 15d-PGJ2: novel modulation mechanism of PPARgamma/RXRalpha function by covalently bound ligands.
T.Waku, T.Shiraki, T.Oyama, K.Morikawa.
 
  ABSTRACT  
 
15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) activates a nuclear receptor heterodimer, peroxisome proliferators-activated receptor gamma (PPARgamma)/ retinoid X receptor (RXRalpha) through covalent binding to Cys285 in PPARgamma ligand-binding domain (LBD). Here, we present the 1.9A crystal structure of C285S mutant LBD complexed with 15d-PGJ(2), corresponding to the non-covalently bound state. The ligand lies adjacent to a hydrogen-bond network around the helix H2 and the nearby beta-sheet. Comparisons with previous structures clarified the relationships between PPARgamma function and conformational alterations of LBD during the process of covalently binding ligands, such as 15d-PGJ(2), and thus suggested a mechanism, by which these ligands modulate PPARgamma/RXRalpha function through conformational changes of the loop following helix H2' and the beta-sheet.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21216727 C.Shionyu-Mitsuyama, T.Waku, T.Shiraki, T.Oyama, T.Shirai, and K.Morikawa (2011).
Detecting structural similarity of ligand interactions in the lipid metabolic system including enzymes, lipid-binding proteins and nuclear receptors.
  Protein Eng Des Sel, 24, 397-403.  
20436486 A.L.Groeger, C.Cipollina, M.P.Cole, S.R.Woodcock, G.Bonacci, T.K.Rudolph, V.Rudolph, B.A.Freeman, and F.J.Schopfer (2010).
Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids.
  Nat Chem Biol, 6, 433-441.  
20673203 A.N.Smirnov (2010).
Lipid signaling in the atherogenesis context.
  Biochemistry (Mosc), 75, 793-810.  
20717101 T.Waku, T.Shiraki, T.Oyama, K.Maebara, R.Nakamori, and K.Morikawa (2010).
The nuclear receptor PPARĪ³ individually responds to serotonin- and fatty acid-metabolites.
  EMBO J, 29, 3395-3407.
PDB codes: 2zk6 3ads 3adt 3adu 3adv 3adw 3adx
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 codes are shown on the right.