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PDBsum entry 2xhd

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protein ligands Protein-protein interface(s) links
Transport protein PDB id
2xhd
Jmol
Contents
Protein chains
261 a.a. *
Ligands
GLU ×2
7T9
SO4 ×5
Waters ×545
* Residue conservation analysis
PDB id:
2xhd
Name: Transport protein
Title: Crystal structure of n-((2s)-5-(6-fluoro-3-pyridinyl)-2,3- dihydro-1h-inden-2-yl)-2-propanesulfonamide in complex with the ligand binding domain of the human glua2 receptor
Structure: Glutamate receptor 2. Chain: a, b. Fragment: ligand binding domain, residues 412-427 and 653-7 synonym: glur-b, glur-k2, glutamate receptor ionotropic amp glua2, ampa-selective glutamate receptor 2. Engineered: yes. Other_details: this is an s1-s2 fusion in which gly 118 and replace a membrane spanning region.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.202     R-free:   0.238
Authors: S.E.Ward,M.Harries,L.Aldegheri,D.Andreotti,S.Ballantine,B.D. A.J.Harris,A.J.Harker,J.Lund,R.Melarange,A.Mingardi,C.Mookh J.Mosley,M.Neve,B.Oliosi,R.Profeta,K.J.Smith,P.W.Smith,S.Sp K.M.Thewlis,S.P.Yusaf
Key ref: S.E.Ward et al. (2010). Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator. J Med Chem, 53, 5801-5812. PubMed id: 20614889 DOI: 10.1021/jm1005429
Date:
14-Jun-10     Release date:   21-Jul-10    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P42262  (GRIA2_HUMAN) -  Glutamate receptor 2
Seq:
Struc:
 
Seq:
Struc:
883 a.a.
261 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transport   1 term 
  Biochemical function     transporter activity     3 terms  

 

 
DOI no: 10.1021/jm1005429 J Med Chem 53:5801-5812 (2010)
PubMed id: 20614889  
 
 
Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator.
S.E.Ward, M.Harries, L.Aldegheri, D.Andreotti, S.Ballantine, B.D.Bax, A.J.Harris, A.J.Harker, J.Lund, R.Melarange, A.Mingardi, C.Mookherjee, J.Mosley, M.Neve, B.Oliosi, R.Profeta, K.J.Smith, P.W.Smith, S.Spada, K.M.Thewlis, S.P.Yusaf.
 
  ABSTRACT  
 
A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21349697 M.L.Mayer (2011).
Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.
  Curr Opin Neurobiol, 21, 283-290.  
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