Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity
(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
- Knecht, Wolfgang LU ; Petersen, Gitte Ebert ; Sandrini, Michael Paolo Bastner LU ; Søndergaard, Leif ; Munch-Petersen, Birgitte LU and Piskur, Jure LU
- publishing date
- 2003-03-15
- 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}}, }