5ZHV

Crystal structure of the PadR-family transcriptional regulator Rv3488 of Mycobacterium tuberculosis H37Rv in complex with zinc ion

Summary for 5ZHV

• Entry DOI: 10.2210/pdb5zhv/pdb
• Descriptor: Transcriptional regulator, ZINC ION (3 entities in total)
• Functional Keywords: dna binding protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 25543.95

Authors

Meera, K.,Pal, R.K.,Arora, A.,Biswal, B.K. (deposition date: 2018-03-13, release date: 2018-10-17, Last modification date: 2023-11-22)

Primary citation

Kumari, M.,Pal, R.K.,Mishra, A.K.,Tripathi, S.,Biswal, B.K.,Srivastava, K.K.,Arora, A.
Structural and functional characterization of the transcriptional regulator Rv3488 ofMycobacterium tuberculosisH37Rv.
Biochem. J., 475:3393-3416, 2018

PubMed Abstract: Rv3488 of H37Rv has been assigned to the phenolic acid decarboxylase repressor (PadR) family of transcriptional regulators that play key roles in multidrug resistance and virulence of prokaryotes. The binding of cadmium, zinc, and several other metals to Rv3488 was discovered and characterized by isothermal titration calorimetery to be an exothermic process. Crystal structures of apo-Rv3488 and Rv3488 in complex with cadmium or zinc ions were determined by X-ray crystallography. The structure of Rv3488 revealed a dimeric protein with N-terminal winged-helix-turn-helix DNA-binding domains composed of helices α1, α2, α3, and strands β1 and β2, with the dimerization interface being formed of helices α4 and α1. The overall fold of Rv3488 was similar to PadR-s2 and metal sensor transcriptional regulators. In the crystal structure of Rv3488-Cd complex, two octahedrally coordinated Cd ions were present, one for each subunit. The same sites were occupied by zinc ions in the structure of Rv3488-Zn, with two additional zinc ions complexed in one monomer. EMSA studies showed specific binding of Rv3488 with its own 30-bp promoter DNA. The functional role of Rv3488 was characterized by expressing the gene under the control of promoter in Expression of Rv3488 increased the intracellular survival of recombinant in murine macrophage cell line J774A.1 and also augmented its tolerance to Cd ions. Overall, the studies show that Rv3488 may have transcription regulation and metal-detoxifying functions and its expression in increases intracellular survival, perhaps by counteracting toxic metal stress.

PubMed: 30266832
DOI: 10.1042/BCJ20180356

Experimental method

X-RAY DIFFRACTION (2.4 Å)