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PDBsum entry 4pt4
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DNA binding protein
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PDB id
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4pt4
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References listed in PDB file
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Key reference
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Title
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Targeting mycobacterium tuberculosis nucleoid-Associated protein hu with structure-Based inhibitors.
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Authors
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T.Bhowmick,
S.Ghosh,
K.Dixit,
V.Ganesan,
U.A.Ramagopal,
D.Dey,
S.P.Sarma,
S.Ramakumar,
V.Nagaraja.
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Ref.
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Nat Commun, 2014,
5,
4124.
[DOI no: ]
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PubMed id
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Abstract
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The nucleoid-associated protein HU plays an important role in maintenance of
chromosomal architecture and in global regulation of DNA transactions in
bacteria. Although HU is essential for growth in Mycobacterium tuberculosis
(Mtb), there have been no reported attempts to perturb HU function with small
molecules. Here we report the crystal structure of the N-terminal domain of HU
from Mtb. We identify a core region within the HU-DNA interface that can be
targeted using stilbene derivatives. These small molecules specifically inhibit
HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The
stilbene inhibitors induce gene expression changes in Mtb that resemble those
induced by HU deficiency. Our results indicate that HU is a potential target for
the development of therapies against tuberculosis.
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