2G9W

Crystal Structure of Rv1846c, a Putative Transcriptional Regulatory Protein of Mycobacterium Tuberculosis

Summary for 2G9W

• Entry DOI: 10.2210/pdb2g9w/pdb
• Descriptor: conserved hypothetical protein, CHLORIDE ION (3 entities in total)
• Functional Keywords: dna-binding domain, bacterial transcription repressor, dna binding protein
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm (Probable): P95163
• Total number of polymer chains: 2
• Total formula weight: 30893.98

Authors

Saul, F.A.,Haouz, A.,Fiez-Vandal, C.,Shepard, W.,Alzari, P.M. (deposition date: 2006-03-07, release date: 2007-03-13, Last modification date: 2024-10-09)

Primary citation

Sala, C.,Haouz, A.,Saul, F.A.,Miras, I.,Rosenkrands, I.,Alzari, P.M.,Cole, S.T.
Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis
Mol.Microbiol., 71:1102-1116, 2009

PubMed Abstract: Comparative genomics with Staphylococcus aureus suggested the existence of a regulatory system governing beta-lactamase (BlaC) production in Mycobacterium tuberculosis. The crystal structure of Rv1846c, a winged helix regulator of previously unknown function, was solved thus revealing strong similarity to the BlaI and MecI repressors of S. aureus, which both respond to beta-lactam treatment. Using chromatin immunoprecipitation and hybridization to microarrays (ChIP-on-chip), the Rv1846c regulon was shown to comprise five separate genomic loci. Two of these mediate responses and resistance to beta-lactam antibiotics (rv1845c, rv1846c-rv1847; blaC-sigC); two encode membrane proteins of unknown function (rv1456c, rv3921c) while the last codes for ATP synthase (rv1303-atpBEFHAGDC-rv1312). The ChIP-on-chip findings were confirmed independently using electrophoretic mobility shift assays, DNAse footprinting and transcript analysis leading to Rv1846c being renamed BlaI. When cells were treated with beta-lactams, BlaI was released from its operator sites causing derepression of the regulon and upregulation of ATP synthase transcription. The existence of a potential regulatory loop between cell wall integrity and ATP production was previously unknown.

PubMed: 19154333
DOI: 10.1111/j.1365-2958.2008.06583.x

Experimental method

X-RAY DIFFRACTION (1.8 Å)