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PDBsum entry 5ig6
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Transcription
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PDB id
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5ig6
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References listed in PDB file
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Key reference
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Title
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A novel phenanthridionone based scaffold as a potential inhibitor of the brd2 bromodomain: crystal structure of the complex.
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Authors
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S.Tripathi,
S.Mathur,
P.Deshmukh,
R.Manjula,
B.Padmanabhan.
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Ref.
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Plos One, 2016,
11,
e0156344.
[DOI no: ]
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PubMed id
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Abstract
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Bromodomain containing proteins recognize the level of histone acetylation and
regulate epigenetically controlled processes like gene transcription and
chromatin modification. The BET (bromodomain and extra-terminal) family
proteins, which are transcriptional co-regulators, have been implicated in the
pathogenesis of cancer, neurodegenerative disorders, and defects in embryonic
stem cell differentiation. Inhibitors selectively targeting the BET bromodomains
can pave the path for new drug discovery against several forms of major
diseases. By a rational structure-based approach, we have identified a new
inhibitor (NSC127133) of the second bromodomain (BD2) of the BET family protein
BRD2 using the NCI Diversity Set III library. A high-resolution crystal
structure of the BRD2-BD2 in complex with this compound and in apo- form is
refined to 0.91 and 0.94 Å, respectively. The compound, which is a
phenanthridinone derivative, binds well to the acetyl-lysine binding pocket of
BD2 and displays significant hydrophobic and hydrophilic interactions. Moreover,
the atomic resolution data obtained in this study allowed us to visualize
certain structural features of BD2 which remained unobserved so far. We propose
that the discovered compound may be a potential molecule to develop a new
library for inhibiting the BRD2-BD2 function.
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