Polyphosphate Kinase 2 (PPK2) Enzymes: Structure, Function, and Roles in Bacterial Physiology and Virulence

Abstract

Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.

Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System

“…PPK, EC 2.7.4.1, is primarily classified into two major families, PPK1 and PPK2. The PPK1 family can catalyze a reversible reaction using ATP and polyP n as substrates to generate ADP and polyP n+1 . , Although both enzyme families, PPK1 and PPK2, can synthesize polyphosphate (polyP), PPK1 primarily uses ATP to synthesize polyP, whereas PPK2 prefers to utilize AMP or ADP . PPK2 can use polyP as a donor to achieve GTP phosphorylation from GDP .…”

Improving Microbial Cell Factory Performance by Engineering SAM Availability

“…The first phosphorylation is catalyzed by adenosine kinase (ADK), which consumes one ATP and releases one ADP. The subsequent two phosphorylation steps are catalyzed by the class II and I of the family 2 polyphosphate kinase (PPK2-II and PPK2-I), respectively, with the consumption of inorganic polyphosphate (polyP) . PPK2-I also regenerates ATP from ADP that is released from the first phosphorylation.…”

Genome-wide screen in human plasma identifies multifaceted complement evasion of Pseudomonas aeruginosa

“…Literature mining indicated that those electron-dense structures could be polyP granules. To cope with an array of different stresses, including nutritional and oxidative stress, P. aeruginosa produces long polyP chains from both GTP and ATP [58,59]. PolyP are then packed into granules to serve as energy and phosphate storage [58,60].…”

“…One stress response in P. aeruginosa is the formation of polyP granules that were observed in several strains upon incubation in plasma. PolyP are involved in many virulence phenotypes including motility and biofilm formation [59], and ppk mutants in Neisseria species were found previously to be strikingly more sensitive to killing by serum [72,73].…”