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Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity

Knecht, Wolfgang LU ; Petersen, Gitte Ebert ; Sandrini, Michael Paolo Bastner LU ; Søndergaard, Leif ; Munch-Petersen, Birgitte LU and Piskur, Jure LU (2003) In Nucleic Acids Research 31(6). p.1665-1672
Abstract

In mammals four deoxyribonucleoside kinases, with a relatively restricted specificity, catalyze the phosphorylation of the four natural deoxyribonucleosides. When cultured mosquito cells, originating from the malaria vector Anopheles gambiae, were examined for deoxyribonucleoside kinase activities, only a single enzyme was isolated. Subsequently, the corresponding gene was cloned and over-expressed. While the mosquito kinase (Ag-dNK) phosphorylated all four natural deoxyribonucleosides, it displayed an unexpectedly higher relative efficiency for the phosphorylation of purine versus pyrimidine deoxyribonucleosides than the fruit fly multisubstrate deoxyribonucleoside kinase (EC 2.7.1.145). In addition, Ag-dNK could also phosphorylate... (More)

In mammals four deoxyribonucleoside kinases, with a relatively restricted specificity, catalyze the phosphorylation of the four natural deoxyribonucleosides. When cultured mosquito cells, originating from the malaria vector Anopheles gambiae, were examined for deoxyribonucleoside kinase activities, only a single enzyme was isolated. Subsequently, the corresponding gene was cloned and over-expressed. While the mosquito kinase (Ag-dNK) phosphorylated all four natural deoxyribonucleosides, it displayed an unexpectedly higher relative efficiency for the phosphorylation of purine versus pyrimidine deoxyribonucleosides than the fruit fly multisubstrate deoxyribonucleoside kinase (EC 2.7.1.145). In addition, Ag-dNK could also phosphorylate some medically interesting nucleoside analogs, like stavudine (D4T), 2-chloro-deoxyadenosine (CdA) and 5-bromo-vinyl-deoxyuridine (BVDU). Although the biological significance of multisubstrate deoxyribonucleoside kinases and their diversity among insects remains unclear, the observed variation provides a whole range of applications, as species specific and highly selective targets for insecticides, they have a potential to be used in the enzymatic production of various (di-)(deoxy-)ribonucleoside monophosphates, and as suicide genes in gene therapy.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Amino Acid Sequence, Animals, Anopheles/cytology, Cell Line, Chromatography, DEAE-Cellulose, Cloning, Molecular, DNA, Complementary/chemistry, Electrophoresis, Polyacrylamide Gel, Kinetics, Molecular Sequence Data, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor)/genetics, Recombinant Proteins/genetics, Sequence Analysis, DNA, Sequence Homology, Substrate Specificity
in
Nucleic Acids Research
volume
31
issue
6
pages
1665 - 1672
publisher
Oxford University Press
external identifiers
  • scopus:0037444079
  • pmid:12626708
ISSN
1362-4962
DOI
10.1093/nar/gkg257
language
English
LU publication?
no
id
7b7a2f03-c00f-464b-a3ca-a857606f4f47
date added to LUP
2020-07-22 14:22:00
date last changed
2024-01-02 15:00:48
@article{7b7a2f03-c00f-464b-a3ca-a857606f4f47,
  abstract     = {{<p>In mammals four deoxyribonucleoside kinases, with a relatively restricted specificity, catalyze the phosphorylation of the four natural deoxyribonucleosides. When cultured mosquito cells, originating from the malaria vector Anopheles gambiae, were examined for deoxyribonucleoside kinase activities, only a single enzyme was isolated. Subsequently, the corresponding gene was cloned and over-expressed. While the mosquito kinase (Ag-dNK) phosphorylated all four natural deoxyribonucleosides, it displayed an unexpectedly higher relative efficiency for the phosphorylation of purine versus pyrimidine deoxyribonucleosides than the fruit fly multisubstrate deoxyribonucleoside kinase (EC 2.7.1.145). In addition, Ag-dNK could also phosphorylate some medically interesting nucleoside analogs, like stavudine (D4T), 2-chloro-deoxyadenosine (CdA) and 5-bromo-vinyl-deoxyuridine (BVDU). Although the biological significance of multisubstrate deoxyribonucleoside kinases and their diversity among insects remains unclear, the observed variation provides a whole range of applications, as species specific and highly selective targets for insecticides, they have a potential to be used in the enzymatic production of various (di-)(deoxy-)ribonucleoside monophosphates, and as suicide genes in gene therapy.</p>}},
  author       = {{Knecht, Wolfgang and Petersen, Gitte Ebert and Sandrini, Michael Paolo Bastner and Søndergaard, Leif and Munch-Petersen, Birgitte and Piskur, Jure}},
  issn         = {{1362-4962}},
  keywords     = {{Amino Acid Sequence; Animals; Anopheles/cytology; Cell Line; Chromatography, DEAE-Cellulose; Cloning, Molecular; DNA, Complementary/chemistry; Electrophoresis, Polyacrylamide Gel; Kinetics; Molecular Sequence Data; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor)/genetics; Recombinant Proteins/genetics; Sequence Analysis, DNA; Sequence Homology; Substrate Specificity}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{6}},
  pages        = {{1665--1672}},
  publisher    = {{Oxford University Press}},
  series       = {{Nucleic Acids Research}},
  title        = {{Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity}},
  url          = {{http://dx.doi.org/10.1093/nar/gkg257}},
  doi          = {{10.1093/nar/gkg257}},
  volume       = {{31}},
  year         = {{2003}},
}