Adenylate kinase and GTP:AMP phosphotransferase of the malarial parasite Plasmodium falciparum

Ulschmid, Julia K.; Rahlfs, Stefan; Schirmer, R. Heiner; Becker, Katja

doi:10.1016/j.molbiopara.2004.04.001

Cited by 15 publications

(16 citation statements)

References 53 publications

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“…One of the main functions of AK3 is to maintain homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates, and it is a central player in cellular energy metabolism [55]. PARP3 is a member of the PARP family catalyzing ADP ribosylation, which is a key post-translational modification step for proteins involved in various signaling pathways such as DNA damage and energy metabolism [56].…”

Section: Discussionmentioning

confidence: 99%

Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

Kim

Park²,

Choi³

et al. 2015

Cell Physiol Biochem

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Background: One of the most interesting issues in obesity research is why certain humans are obesity-prone (OP) while others are obesity-resistant (OR) upon exposure to a high-calorie diet. However, the pathways responsible for these phenotypic differences are still largely unknown. Methods: In order to discover marker molecules determining susceptibility and/or resistance to obesity in response to high fat diet (HFD) or anti-obesity herbal medicine (TH), we conducted comparative proteomic analysis of white adipose tissue (WAT) from OP, OR, as well as TH-treated mice. Results: OP mice fed HFD gained approximately 33% more body weight than OR mice, and TH significantly reduced body weight gain in HFD-fed mice by 30%. These mice were further subjected to proteomic analysis using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Proteomic data revealed 59 spots that were differentially regulated from a total of 1,045 matched spots, and 57 spots of these were identified as altered WAT proteins between OP and OR mice by peptide mass finger printing. Interestingly, 45 proteins were similarly regulated in OR mice in response to TH treatment. Of these, 10 proteins have already been recognized in the context of obesity; however, other proteins involved in obesity susceptibility or resistance were identified for the first time in the present study. Conclusion: Our results suggest that TH actively contributed to body weight reduction in HFD-fed obese mice by altering protein regulation in WAT, and it was also found that TH-responsive proteins can be used as potent molecules for obesity treatment.

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Section: Discussionmentioning

confidence: 99%

Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

Kim

Park²,

Choi³

et al. 2015

Cell Physiol Biochem

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“…The pH optimum of the His-tagged recombinant yeast AK3 was at about 8.5 (Schricker et al 1995). Recently, Plasmodium falciparum AK3 was identified and the pH optimum was found to be 6.0 (Ulschmid et al 2004). The pH optima of AK3 from organisms vary from acid to alkaline.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning and characterization of a novel adenylate kinase 3 gene from Clonorchis sinensis

Guang

et al. 2005

Parasitol Res

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Adenylate kinase (AK) is a ubiquitous enzyme that contributes to the homeostasis of adenine nucleotides in living cells. AK catalyzes reversible high energy phosphoryl transfer reactions between ATP (or GTP) and AMP to generate ADP (or GDP). From a Clonorchis sinensis adult worm cDNA library, we isolated a cDNA clone encoding a novel AK3 isozyme. The 956 bp cDNA encodes a putative protein of 228 amino acids with a predicted molecular mass of 26.2 kDa. The recombinant CsAK3 protein produced in Escherichia coli can be refolded into a functional protein with AK3 activity. The optimum pH and temperature for the enzyme are 8.5 and 40 degrees C, respectively. The calculated activation energy is 56.04 kJ mol-1. The Km of the CsAK3 for AMP and GTP are 118 microM and 359 microM, respectively. CsAK3 is inhibited by Ap5A (>70% inhibition by 2.0 mM AP5A). Ap5A may be a potential lead compound acting on C. sinensis in which AK3 as a drug target.

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“…In contrast, studies with GTP:AMP phosphotransferases have so far been confined mostly to their mitochondrial localization and substrate specificity and kinetic characterization of various mutants (9,10,12,23,34). The molecular properties of the GTP: AMP phosphotransferase, particularly in the context of protein folding and thermal tolerance, have not been studied.…”

Section: Discussionmentioning

confidence: 99%

A GTP:AMP Phosphotransferase, Adk2p, in Saccharomyces cerevisiae

Gordon

Amutha

et al. 2005

Journal of Biological Chemistry

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Adenylate kinases participate in maintaining the homeostasis of cellular nucleotides. Depending on the yeast strains, the GTP:AMP phosphotransferase is encoded by the nuclear gene ADK2 with or without a single base pair deletion/insertion near the 3 end of the open reading frame, and the corresponding protein exists as either Adk2p (short) or Adk2p (long) in the mitochondrial matrix. These two forms are identical except that the three C-terminal residues of Adk2p (short) are changed in Adk2p (long), and the latter contains an additional nine amino acids at the C terminus of the protein. The short form of Adk2p has so far been considered to be inactive (Schricker, R., Magdolen, V., Strobel, G., Bogengruber, E., Breitenbach, M., and Bandlow, W. (1995) J. Biol. Chem. 270, 31103-31110). Using purified proteins, we show that at the physiological temperature for yeast growth (30°C), both short and long forms of Adk2p are enzymatically active. However, in contrast to the short form, Adk2p (long) is quite resistant to thermal inactivation, urea denaturation, and degradation by trypsin. Unfolding of the long form by high concentrations of urea greatly stimulated its import into isolated mitochondria. Using an integration-based gene-swapping approach, we found that regardless of the yeast strains used, the steady state levels of endogenous Adk2p (long) in mitochondria were 5-10-fold lower compared with those of Adk2p (short). Together, these results suggest that the modified C-terminal domain in Adk2p (long) is not essential for enzyme activity, but it contributes to and strengthens protein folding and/or stability and is particularly important for maintaining enzyme activity under stress conditions. Cellular homeostasis of nucleotides is essential for numerous important biological processes. Among several enzymes that participate in maintaining cellular levels of nucleotides are adenylate kinases, which catalyze the reaction ATP (or GTP) ϩ AMP N ADP (or GDP) ϩ ADP (1-3). These kinases provide ADP for oxidative phosphorylation (4) and also control the intracellular AMP level, which serves as a highly sensitive sensor of cellular energy status. Under stress conditions, increased levels of AMP trigger the AMP-activated protein kinase cascade to switch on catabolic pathways that generate ATP while switching off anabolic processes that consume ATP (5, 6). Adenylate kinases therefore occupy a central position in many cellular functions under normal as well as stress conditions. Although ATP-specific adenylate kinases from different organisms have been extensively studied, not much is known about the GTP-specific isoforms.Adenylate kinase in Escherichia coli is indispensable for growth (7). In mammalian cells, at least three (AK1, AK2, and AK3) isoforms of adenylate kinase exist (8 -11). AK1 and AK2 use Mg 2ϩ ATP as the high energy phosphate donor, whereas AK3 is a GTP:AMP phosphotransferase and uses GTP instead of ATP as a phosphoryl donor. AK1 and AK3 are localized to the cytosol and mitochondrial matrix, respectively. In con...

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Adenylate kinase and GTP:AMP phosphotransferase of the malarial parasite Plasmodium falciparum

Cited by 15 publications

References 53 publications

Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

Molecular cloning and characterization of a novel adenylate kinase 3 gene from Clonorchis sinensis

A GTP:AMP Phosphotransferase, Adk2p, in Saccharomyces cerevisiae

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