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PDBsum entry 2xhd
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Transport protein
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PDB id
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2xhd
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Contents |
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* Residue conservation analysis
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PDB id:
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Transport protein
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Title:
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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
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Structure:
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Glutamate receptor 2. Chain: a, b. Fragment: ligand binding domain, residues 412-427 and 653-796. Synonym: glur-b, glur-k2, glutamate receptor ionotropic ampa 2, glua2, ampa-selective glutamate receptor 2. Engineered: yes. Other_details: this is an s1-s2 fusion in which gly 118 and thr 119 replace a membrane spanning region.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.80Å
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R-factor:
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0.202
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R-free:
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0.238
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Authors:
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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
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Key ref:
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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:
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Date:
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14-Jun-10
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Release date:
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21-Jul-10
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PROCHECK
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Headers
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References
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P42262
(GRIA2_HUMAN) -
Glutamate receptor 2 from Homo sapiens
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Seq:
Struc:
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883 a.a.
261 a.a.*
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Key: |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 7 residue positions (black
crosses)
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J Med Chem
53:5801-5812
(2010)
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PubMed id:
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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.
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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.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.L.Mayer
(2011).
Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.
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Curr Opin Neurobiol,
21,
283-290.
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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.
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Links
