Positively-Charged Semi-Tunnel Is a Structural and Surface Characteristic of Polyphosphate-Binding Proteins: An In-Silico Study

Wei, Zheng Zachory; Vatcher, Greg; Tin, Alvin Hok Yan; Teng, Jun Lin; Wang, Juan; Cui, Qing Hua; Chen, Jian Guo; Yu, Albert Cheung Hoi

doi:10.1371/journal.pone.0123713

Cited by 9 publications

(7 citation statements)

References 64 publications

(50 reference statements)

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“…233 The existence of such a tunnel-like structure has also been proposed for certain polyP-binding proteins. 234 Also an enzyme related to the yeast PPN1 has been partially purified from rat and bovine brain 220 but not further studied. The DDP1 belongs to the Nudix hydrolase family and seems to be primarily involved in inositol pyrophosphate metabolism but can also act as a polyP-hydrolyzing endopolyphosphatase.…”

Section: Polyp Metabolism In Prokaryotic and Eukaryotic Cells: Enzymesmentioning

confidence: 99%

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

2019

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Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that are present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy as polyP. However, the function and metabolism of this long-neglected polymer are scarcely known, especially in higher eukaryotes. In recent years, interest in polyP experienced a renaissance, beginning with the discovery of polyP as phosphate source in bone mineralization. Later, two discoveries placed polyP into the focus of regenerative medicine applications. First, polyP shows morphogenetic activity, i.e., induces cell differentiation via gene induction, and, second, acts as an energy storage and donor in the extracellular space. Studies on acidocalcisomes and mitochondria provided first insights into the enzymatic basis of eukaryotic polyP formation. In addition, a concerted action of alkaline phosphatase and adenylate kinase proved crucial for ADP/ATP generation from polyP. PolyP added extracellularly to mammalian cells resulted in a 3-fold increase of ATP. The importance and mechanism of this phosphotransfer reaction for energy-consuming processes in the extracellular matrix are discussed. This review aims to give a critical overview about the formation and function of this unique polymer that is capable of storing (bio)chemically useful energy.

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Section: Polyp Metabolism In Prokaryotic and Eukaryotic Cells: Enzymesmentioning

confidence: 99%

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

2019

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“…PolyP 15 , in turn, preferentially binds in a double conformation (Fig. C), which was recently suggested for other proteins that bind polyPs (Wei et al ., ). Ion‐dipole‐type interactions were observed with amino acids in the upper part of the site, such as Thr61 and Met59, and also with amino acid residues in the lowest part of the site, such as Asn201 and His81, close to Cys83 in the dimer interface, which may have additional implications for the stability of the interactions.…”

Section: Resultsmentioning

confidence: 97%

A soluble inorganic pyrophosphatase from the cattle tick Rhipicephalus microplus capable of hydrolysing polyphosphates

Cruz

Costa²,

Machado³

et al. 2017

Insect Molecular Biology

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Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the cell type. In eukaryotic organisms, polyphosphates have been investigated mainly in mammalian cells, and only a few studies have addressed arthropods. Pyrophosphatases have been shown to regulate polyphosphate metabolism. However, these studies were restricted to trypanosomatids. Here we focus on the tick Rhipicephalus microplus, a haematophagous ectoparasite that is highly harmful to cattle. We produced a recombinant R. microplus pyrophosphatase (rRmPPase) with the aim of investigating its kinetic parameters using polyphosphates as substrate. Molecular docking assays of RmPPase with polyphosphates were also carried out. The kinetic and Hill coefficient parameters indicated that rRmPPase has a greater affinity, higher catalytic efficiency and increased cooperativity for sodium phosphate glass type 15 (polyP ) than for sodium tripolyphosphate (polyP ). Through molecular docking, we found that polyP binds close to the Mg atoms in the catalytic region of the protein, participating in their coordination network, whereas polyP interactions involve negatively charged phosphate groups and basic amino acid residues, such as Lys56, Arg58 and Lys193; polyP has a more favourable theoretical binding affinity than polyP , thus supporting the kinetic data. This study shows, for the first time in arthropods, a pyrophosphatase with polyphosphatase activity, suggesting its participation in polyphosphate metabolism.

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“…The first report came from Vandegrift and Evans [95] by the demonstration that polyP can bind to protein(s) in human serum. Later those data were impressively extended with the demonstration that bacterial enzymes strongly associate to polyP [96]. Certainly the strengths of the interactions are dependent on pH, ionic strength of the medium and the chain length of the polyP.…”

Section: Uptake Of Polyp Receptor-mediated Endocytosismentioning

confidence: 95%

Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications

Wang

Schröder

Müller

2015

Biotechnology Journal

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In animals, energy-rich molecules like ATP are generated in the intracellular compartment from metabolites, e.g. glucose, taken up by the cells. Recent results revealed that inorganic polyphosphates (polyP) can provide an extracellular system for energy transport and delivery. These polymers of multiple phosphate units, linked by high-energy phosphoanhydride bonds, use blood platelets as transport vehicles to reach their target cells. In this review it is outlined how polyP affects cell metabolism. It is discussed that polyP influences cell activity in a dual way: (i) as a metabolic fuel transferring metabolic energy through the extracellular space; and (ii) as a signaling molecule that amplifies energy/ATP production in mitochondria. Several metabolic pathways are triggered by polyP, among them biomineralization/hydroxyapatite formation onto bone cells. The accumulation of polyP in the platelets allows long-distance transport of the polymer in the extracellular space. The discovery of polyP as metabolic fuel and signaling molecule initiated the development of novel techniques for encapsulation of polyP into nanoparticles. They facilitate cellular uptake of the polymer by receptor-mediated endocytosis and allow the development of novel strategies for therapy of metabolic diseases associated with deviations in energy metabolism or mitochondrial dysfunctions.

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Positively-Charged Semi-Tunnel Is a Structural and Surface Characteristic of Polyphosphate-Binding Proteins: An In-Silico Study

Cited by 9 publications

References 64 publications

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

A soluble inorganic pyrophosphatase from the cattle tick Rhipicephalus microplus capable of hydrolysing polyphosphates

Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications

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