PDBsum entry 4pt4

DNA binding protein

PDB id: 4pt4

Contents

Protein chains

99 a.a.

Ligands

FMT ×4

Waters ×86

PDB id:

4pt4

Name:

DNA binding protein

Title:

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]

Structure:

DNA-binding protein hu homolog. Chain: a, b. Fragment: n terminal unp residues 1-99 (dimerization domain and DNA binding domain). Synonym: histone-like protein. Engineered: yes

Source:

Mycobacterium tuberculosis h37ra. Organism_taxid: 419947. Gene: hupb, mra_3015. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.04Å R-factor: 0.191 R-free: 0.249

Authors:

T.Bhowmick,U.A.Ramagopal,S.Ghosh,V.Nagaraja,S.Ramakumar

Key ref:

T.Bhowmick et al. (2014). Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors. Nat Commun, 5, 4124. PubMed id: 24916461 DOI: 10.1038/ncomms5124

Date:

10-Mar-14 Release date: 21-May-14

Supersedes:

3c4i

Protein chains

A5U6Z7  (A5U6Z7_MYCTA) -  DNA-binding protein HupB from Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)

Seq: 214 a.a.

Struc: 99 a.a.

DOI no: 10.1038/ncomms5124

Nat Commun 5:4124 (2014)

PubMed id: 24916461

Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors.

T.Bhowmick, S.Ghosh, K.Dixit, V.Ganesan, U.A.Ramagopal, D.Dey, S.P.Sarma, S.Ramakumar, V.Nagaraja.

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.