4PT4

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]

Replaces:  3C4I

Summary for 4PT4

• Entry DOI: 10.2210/pdb4pt4/pdb
• Related: 4DKY
• Descriptor: DNA-binding protein HU homolog, FORMIC ACID (3 entities in total)
• Functional Keywords: dimerization by four helix bundle interaction, dna condensation, dna-binding, dna binding protein
• Biological source: Mycobacterium tuberculosis H37Ra
• Total number of polymer chains: 2
• Total formula weight: 21528.53

Authors

Bhowmick, T.,Ramagopal, U.A.,Ghosh, S.,Nagaraja, V.,Ramakumar, S. (deposition date: 2014-03-10, release date: 2014-05-21, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.04 Å)