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PDBsum entry 1x7b
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Transcription
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PDB id
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1x7b
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References listed in PDB file
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Key reference
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Title
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Structure-Based design of estrogen receptor-Beta selective ligands.
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Authors
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E.S.Manas,
R.J.Unwalla,
Z.B.Xu,
M.S.Malamas,
C.P.Miller,
H.A.Harris,
C.Hsiao,
T.Akopian,
W.T.Hum,
K.Malakian,
S.Wolfrom,
A.Bapat,
R.A.Bhat,
M.L.Stahl,
W.S.Somers,
J.C.Alvarez.
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Ref.
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J Am Chem Soc, 2004,
126,
15106-15119.
[DOI no: ]
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PubMed id
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Abstract
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We present the structure-based optimization of a series of estrogen
receptor-beta (ERbeta) selective ligands. X-ray cocrystal structures of these
ligands complexed to both ERalpha and ERbeta are described. We also discuss how
molecular modeling was used to take advantage of subtle differences between the
two binding cavities in order to optimize selectivity for ERbeta over ERalpha.
Quantum chemical calculations are utilized to gain insight into the mechanism of
selectivity enhancement. Despite only two relatively conservative residue
substitutions in the ligand binding pocket, the most selective compounds have
greater than 100-fold selectivity for ERbeta relative to ERalpha when measured
using a competitive radioligand binding assay.
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