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A Mycobacterial Cyclic AMP Phosphodiesterase That Moonlights as a Modifier of Cell Wall Permeability

Podobnik, Marjetka and Tyagi, Richa and Matange, Nishad and Dermol, Urska and Gupta, Arun K and Mattoo, Rohini and Seshadri, Kothandaraman and Visweswariah, Sandhya S (2009) A Mycobacterial Cyclic AMP Phosphodiesterase That Moonlights as a Modifier of Cell Wall Permeability. In: Journal of biological chemistry, 284 (47). pp. 32846-32857.

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Mycobacterium tuberculosis utilizes many mechanisms to establish itself within the macrophage, and bacterially derived cAMP is important in modulating the host cellular response. Although the genome of M. tuberculosis is endowed with a number of mammalian-like adenylyl cyclases, only a single cAMP phosphodiesterase has been identified that can decrease levels of cAMP produced by the bacterium. We present the crystal structure of the full-length and sole cAMP phosphodiesterase, Rv0805, found in M. tuberculosis, whose orthologs are present only in /the genomes of slow growing and pathogenic mycobacteria. The dimeric core catalytic domain of Rv0805 adopts a metallophosphoesterase fold, and the C-terminal region builds the active site and contributes to multiple substrate utilization.Localization of Rv0805 to the cell wall is dependent on its C terminus, and expression of either wild type or mutationally inactivated Rv0805 in M. smegmatis alters cell permeability to hydrophobic cytotoxic compounds. Rv0805 may therefore play a key role in the pathogenicity of mycobacteria, not only by hydrolyzing bacterial cAMP, but also by moonlighting as a protein that can alter cell wall functioning.

Item Type: Journal Article
Publication: Journal of biological chemistry
Publisher: The American Society for Biochemistry and Molecular Biology
Additional Information: copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 12 Jan 2010 06:32
Last Modified: 19 Sep 2010 05:53
URI: http://eprints.iisc.ac.in/id/eprint/25157

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