5zhv
Crystal structure of the PadR-family transcriptional regulator Rv3488 of Mycobacterium tuberculosis H37Rv in complex with zinc ion
Structural highlights
FunctionCDDTR_MYCTU May have transcription regulation and metal-detoxifying functions through which it may enhance intracellular survival of mycobacteria. Binds to its own promoter region and to the Rv1999c promoter region. It displays strong affinity for cadmium ions, but can also bind zinc, manganese and nickel. Expression increases the intracellular survival of recombinant M. smegmatis in murine macrophage cell line and increases its tolerance to cadmium ions.[1] Publication Abstract from PubMedRv3488 of Mycobacterium tuberculosis 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 alpha1, alpha2, alpha3, and strands beta1 and beta2, with the dimerization interface being formed of helices alpha4 and alpha1. 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(2+) 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 rv3488 gene under the control of hsp60 promoter in Mycobacterium smegmatis Expression of Rv3488 increased the intracellular survival of recombinant M. smegmatis in murine macrophage cell line J774A.1 and also augmented its tolerance to Cd(2+) ions. Overall, the studies show that Rv3488 may have transcription regulation and metal-detoxifying functions and its expression in M. smegmatis increases intracellular survival, perhaps by counteracting toxic metal stress. Structural and functional characterization of the transcriptional regulator Rv3488 of Mycobacterium tuberculosis H37Rv.,Kumari M, Pal RK, Mishra AK, Tripathi S, Biswal BK, Srivastava KK, Arora A Biochem J. 2018 Nov 9;475(21):3393-3416. doi: 10.1042/BCJ20180356. PMID:30266832[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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