The Non-catalytic “Cap Domain” of a Mycobacterial Metallophosphoesterase Regulates Its Expression and Localization in the Cell

Abstract

Background: Metallophosphoesterases possess unique, poorly characterized cap domains located at the entrance to the active site. Results: The C terminus of the cap domain of the Rv0805 metallophosphoesterase modulates its expression, cell envelope localization, and biological functions. Conclusion:The functions of the Rv0805 metallophosphoesterase are regulated by the cap domain. Significance: Cap domains may provide catalysis-independent features to metallophosphoesterases that shape their cellular functions.

CaII Binding Regulates and Dominates the Reactivity of a Transition‐Metal‐Ion‐Dependent Diesterase from Mycobacterium tuberculosis

“…[5,6] Am ore recently identified dinuclear metallohydrolase is the protein Rv0805 from Mycobacterium tuberculosis,aphosphodiesterase that utilizes substrates, such as cyclic nucleotides (e.g.,3 ',5'-cyclic adenosine monophosphate (cAMP) and 2',3'-cAMP),a nd which is believed to be involved in bacterial signal transductionb yr egulating the intracellular concentrations of cyclic nucleotides. [7][8][9][10][11] Phenotypic profiling recently identified Rv0805a sa ne ssential enzyme for mycobacterial growth and hencet his enzyme may provide an alternative targetf or much needed new chemotherapeutics to combat multi-drug-resistant M. tuberculosis. [11] Our initial motivation to study Rv0805w as driven by the ambition to develop an enzyme-based system that may be used for applicationsi nb ioremediation (i.e.,t he removal of pesticides from the environment).…”

“…[7][8][9][10][11] Phenotypic profiling recently identified Rv0805a sa ne ssential enzyme for mycobacterial growth and hencet his enzyme may provide an alternative targetf or much needed new chemotherapeutics to combat multi-drug-resistant M. tuberculosis. [11] Our initial motivation to study Rv0805w as driven by the ambition to develop an enzyme-based system that may be used for applicationsi nb ioremediation (i.e.,t he removal of pesticides from the environment). In previouss tudies we investigated the physicochemicalp roperties of ag lycerophosphodiesterase from Enterobactera erogenes (namely,G pdQ), an enzyme that is highly promiscuousw ith respectt os ubstrates it can metabolize and the metal ions that promote catalytic activity.…”

Eukaryotic-Type Ser/Thr Protein Kinase Mediated Phosphorylation of Mycobacterial Phosphodiesterase Affects its Localization to the Cell Wall

“…The mPDE has already been characterized and its structure was determined using X-ray crystallographic studies (Shenoy et al, 2007 ). While its N-terminal catalytic domain is responsible for the enzyme activity, the C-terminal region mediates its localization (Podobnik et al, 2009 ; Matange et al, 2014 ).…”

BacillussubtilisPhosphodiesterasePhoD

“…Assuming that this has a regulatory role in PhoD, a regulatory repression loop has been reported acting on the Fe 2+ in the mammalian PAPs. 33 However, this is unlikely to be fulfilling the same function, and the PhoD α-helix positioning appears more akin to that in the Matange et al 30 study of M. tuberculosis.…”

“…A Cterminal α-helix is also present in a metallophosphoesterase from Mycobacterium tuberculosis. Matange et al 30 report that this α-helix plays a role in the localization of the phosphatase to the cell wall. It is interesting to speculate that the C-terminal α-helix of PhoD has a similar function in the utilization of cell wall teichoic acids.…”