The Two PPX-GppA Homologues from Mycobacterium tuberculosis Have Distinct Biochemical Activities

• DOI: 10.1371/journal.pone.0042561
• Publication Date: 2012-08-03T23:03:06Z
• Authors: Mei Y. Choi; Ying Wang; Leo L. Y. Wong; Bing-tai Lu; Wen-yang Chen; Jian-Dong Huang; Julian A. Tanner; Rory M. Watt
• Keywords: Stringent response

Inorganic polyphosphate (poly-P), guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp) are ubiquitous in bacteria. These molecules play a variety of important physiological roles associated with stress resistance, persistence, virulence. In the bacterial pathogen Mycobacterium tuberculosis, identities proteins responsible for metabolism (p)ppGpp remain to be fully established. M. tuberculosis encodes two PPX-GppA homologues, Rv0496 (MTB-PPX1) Rv1026, which share significant sequence similarity exopolyphosphatase (PPX) 5′-phosphohydrolase (GPP) proteins. Here we delineate respective biochemical activities Rv1026 benchmark these against PPX GPP from Escherichia coli. We demonstrate that functions as an exopolyphosphatase, showing distinct preference relatively short-chain poly-P substrates. contrast, has no detectable activities. Analogous E. coli enzymes, inhibited by pppGpp and, lesser extent, ppGpp alarmones, produced during stringent response. However, neither nor have ability hydrolyze ppGpp; reaction catalyzed GPP. Both modest ATPase extent ADPase alarmones inhibit Rv0496. conclude family may not possess all catalytic implied their name involved metabolic pathways.