Cleavage of DNA and nuclease properties of Plasmodium Nucleoside Diphosphate Kinase

Abdullah Al-Taher, Mahmoud Kandeel, Hye-Sook Kim, Yukio Kitade

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The identification of extra-functional activities of enzymes is an attractive strategy for development of new antiparasitic drugs. In this study, the nuclease properties of Plasmodium Nucleoside Diphosphate Kinase (PfNDK) were demonstrated. The classical effect of PfNDK is the production of nucleotides for DNA/RNA synthesis. Such new nuclease activity of PfNDK implies the incrimination of the enzyme in functions other than its classical kinase activity. Such functions include apoptosis, regulation of cell cycle, cell division and repair of DNA damage. We have investigated the nuclease activity of Plasmodium falciparum Nucleoside Diphosphate Kinase (PfNDK). The nature of the nucleotide sequence and the length of the DNA substrate were critical factors in PfNDK’s nuclease activity. The PfNDK was unable to bind to oligonucleotides, although it formed aggregates with oligonucleotides that contained repeated pyrimidine nucleotides in their sequence. The enzyme was unable to cleave a supercoiled plasmid, whereas DNA substrates of various lengths were cleaved in a time- and concentration-dependent manner. Furthermore, ATP at a concentration of 1 mM was able to inhibit the nuclease activity. These data is valuable in highlighting the possible role of PfNDK in cellular functions other than its classical nucleotide kinase activity. Specific PfNDK inhibition is expected to modulate parasites cell cycle and induction of apoptosis.

Original languageEnglish
Pages (from-to)334-339
Number of pages6
JournalInternational Journal of Pharmacology
Volume10
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Nucleoside-Diphosphate Kinase
Plasmodium
Deoxyribonucleases
Plasmodium falciparum
Oligonucleotides
DNA
Cell Cycle
Phosphotransferases
Enzymes
Nucleotides
Pyrimidine Nucleotides
Apoptosis
Antiparasitic Agents
Cell Division
DNA Damage
Parasites
Plasmids
Adenosine Triphosphate
RNA

Keywords

  • DNA binding
  • Malaria
  • Nuclease
  • Nucleoside diphosphate kinase
  • Plasmodium

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cleavage of DNA and nuclease properties of Plasmodium Nucleoside Diphosphate Kinase. / Al-Taher, Abdullah; Kandeel, Mahmoud; Kim, Hye-Sook; Kitade, Yukio.

In: International Journal of Pharmacology, Vol. 10, No. 6, 2014, p. 334-339.

Research output: Contribution to journalArticle

Al-Taher, Abdullah ; Kandeel, Mahmoud ; Kim, Hye-Sook ; Kitade, Yukio. / Cleavage of DNA and nuclease properties of Plasmodium Nucleoside Diphosphate Kinase. In: International Journal of Pharmacology. 2014 ; Vol. 10, No. 6. pp. 334-339.
@article{fa4369f9d8dd422f807be15470dd6b9b,
title = "Cleavage of DNA and nuclease properties of Plasmodium Nucleoside Diphosphate Kinase",
abstract = "The identification of extra-functional activities of enzymes is an attractive strategy for development of new antiparasitic drugs. In this study, the nuclease properties of Plasmodium Nucleoside Diphosphate Kinase (PfNDK) were demonstrated. The classical effect of PfNDK is the production of nucleotides for DNA/RNA synthesis. Such new nuclease activity of PfNDK implies the incrimination of the enzyme in functions other than its classical kinase activity. Such functions include apoptosis, regulation of cell cycle, cell division and repair of DNA damage. We have investigated the nuclease activity of Plasmodium falciparum Nucleoside Diphosphate Kinase (PfNDK). The nature of the nucleotide sequence and the length of the DNA substrate were critical factors in PfNDK’s nuclease activity. The PfNDK was unable to bind to oligonucleotides, although it formed aggregates with oligonucleotides that contained repeated pyrimidine nucleotides in their sequence. The enzyme was unable to cleave a supercoiled plasmid, whereas DNA substrates of various lengths were cleaved in a time- and concentration-dependent manner. Furthermore, ATP at a concentration of 1 mM was able to inhibit the nuclease activity. These data is valuable in highlighting the possible role of PfNDK in cellular functions other than its classical nucleotide kinase activity. Specific PfNDK inhibition is expected to modulate parasites cell cycle and induction of apoptosis.",
keywords = "DNA binding, Malaria, Nuclease, Nucleoside diphosphate kinase, Plasmodium",
author = "Abdullah Al-Taher and Mahmoud Kandeel and Hye-Sook Kim and Yukio Kitade",
year = "2014",
doi = "10.3923/ijp.2014.334.339",
language = "English",
volume = "10",
pages = "334--339",
journal = "International Journal of Pharmacology",
issn = "1811-7775",
publisher = "Asian Network for Scientific Information",
number = "6",

}

TY - JOUR

T1 - Cleavage of DNA and nuclease properties of Plasmodium Nucleoside Diphosphate Kinase

AU - Al-Taher, Abdullah

AU - Kandeel, Mahmoud

AU - Kim, Hye-Sook

AU - Kitade, Yukio

PY - 2014

Y1 - 2014

N2 - The identification of extra-functional activities of enzymes is an attractive strategy for development of new antiparasitic drugs. In this study, the nuclease properties of Plasmodium Nucleoside Diphosphate Kinase (PfNDK) were demonstrated. The classical effect of PfNDK is the production of nucleotides for DNA/RNA synthesis. Such new nuclease activity of PfNDK implies the incrimination of the enzyme in functions other than its classical kinase activity. Such functions include apoptosis, regulation of cell cycle, cell division and repair of DNA damage. We have investigated the nuclease activity of Plasmodium falciparum Nucleoside Diphosphate Kinase (PfNDK). The nature of the nucleotide sequence and the length of the DNA substrate were critical factors in PfNDK’s nuclease activity. The PfNDK was unable to bind to oligonucleotides, although it formed aggregates with oligonucleotides that contained repeated pyrimidine nucleotides in their sequence. The enzyme was unable to cleave a supercoiled plasmid, whereas DNA substrates of various lengths were cleaved in a time- and concentration-dependent manner. Furthermore, ATP at a concentration of 1 mM was able to inhibit the nuclease activity. These data is valuable in highlighting the possible role of PfNDK in cellular functions other than its classical nucleotide kinase activity. Specific PfNDK inhibition is expected to modulate parasites cell cycle and induction of apoptosis.

AB - The identification of extra-functional activities of enzymes is an attractive strategy for development of new antiparasitic drugs. In this study, the nuclease properties of Plasmodium Nucleoside Diphosphate Kinase (PfNDK) were demonstrated. The classical effect of PfNDK is the production of nucleotides for DNA/RNA synthesis. Such new nuclease activity of PfNDK implies the incrimination of the enzyme in functions other than its classical kinase activity. Such functions include apoptosis, regulation of cell cycle, cell division and repair of DNA damage. We have investigated the nuclease activity of Plasmodium falciparum Nucleoside Diphosphate Kinase (PfNDK). The nature of the nucleotide sequence and the length of the DNA substrate were critical factors in PfNDK’s nuclease activity. The PfNDK was unable to bind to oligonucleotides, although it formed aggregates with oligonucleotides that contained repeated pyrimidine nucleotides in their sequence. The enzyme was unable to cleave a supercoiled plasmid, whereas DNA substrates of various lengths were cleaved in a time- and concentration-dependent manner. Furthermore, ATP at a concentration of 1 mM was able to inhibit the nuclease activity. These data is valuable in highlighting the possible role of PfNDK in cellular functions other than its classical nucleotide kinase activity. Specific PfNDK inhibition is expected to modulate parasites cell cycle and induction of apoptosis.

KW - DNA binding

KW - Malaria

KW - Nuclease

KW - Nucleoside diphosphate kinase

KW - Plasmodium

UR - http://www.scopus.com/inward/record.url?scp=84908112185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908112185&partnerID=8YFLogxK

U2 - 10.3923/ijp.2014.334.339

DO - 10.3923/ijp.2014.334.339

M3 - Article

AN - SCOPUS:84908112185

VL - 10

SP - 334

EP - 339

JO - International Journal of Pharmacology

JF - International Journal of Pharmacology

SN - 1811-7775

IS - 6

ER -