4DKY

Crystal structure Analysis of N terminal region containing the dimerization domain and DNA binding domain of HU protein(Histone like protein-DNA binding) from Mycobacterium tuberculosis [H37Ra]

4DKY の概要

• エントリーDOI: 10.2210/pdb4dky/pdb
• 関連するPDBエントリー: 3C4I
• 分子名称: DNA-binding protein HU homolog, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: nucleoid associated protein, nucleoid architecture, histone-like, hu, hu-ihf fold, genome compaction, gene regulation, dna binding protein
• 由来する生物種: Mycobacterium tuberculosis H37Ra
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23306.30

構造登録者

Bhowmick, T.,Ramagopal, U.A.,Ghosh, S.,Nagaraja, V.,Ramakumar, S. (登録日: 2012-02-05, 公開日: 2013-02-06, 最終更新日: 2023-11-08)

主引用文献

Bhowmick, T.,Ghosh, S.,Dixit, K.,Ganesan, V.,Ramagopal, U.A.,Dey, D.,Sarma, S.P.,Ramakumar, S.,Nagaraja, V.
Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors
Nat Commun, 5:4124-4124, 2014

PubMed Abstract: 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.

PubMed: 24916461
DOI: 10.1038/ncomms5124

実験手法

X-RAY DIFFRACTION (2.478 Å)