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Structural basis for substrate specificities of cellular deoxyribonucleoside kinases

Johansson, K ; Ramaswamy, S ; Ljungcrantz, C ; Knecht, W LU ; Piskur, J LU ; Munch-Petersen, B LU ; Eriksson, S and Eklund, Hans (2001) In Nature Structural Biology 8(7). p.616-620
Abstract

Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an... (More)

Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.

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author
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publishing date
type
Contribution to journal
publication status
published
keywords
Adenosine Triphosphate/metabolism, Amino Acid Sequence, Animals, Binding Sites, Crystallography, X-Ray, Deoxycytidine/metabolism, Drosophila melanogaster/enzymology, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Phosphotransferases (Alcohol Group Acceptor)/chemistry, Protein Conformation, Sequence Alignment, Structure-Activity Relationship, Substrate Specificity
in
Nature Structural Biology
volume
8
issue
7
pages
616 - 620
publisher
Nature Publishing Group
external identifiers
  • scopus:0034964197
  • pmid:11427893
ISSN
1072-8368
DOI
10.1038/89661
language
English
LU publication?
no
id
ebd86e8a-d67d-4365-a128-81c6240faafe
date added to LUP
2020-07-22 14:28:49
date last changed
2025-04-19 06:22:53
@article{ebd86e8a-d67d-4365-a128-81c6240faafe,
  abstract     = {{<p>Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.</p>}},
  author       = {{Johansson, K and Ramaswamy, S and Ljungcrantz, C and Knecht, W and Piskur, J and Munch-Petersen, B and Eriksson, S and Eklund, Hans}},
  issn         = {{1072-8368}},
  keywords     = {{Adenosine Triphosphate/metabolism; Amino Acid Sequence; Animals; Binding Sites; Crystallography, X-Ray; Deoxycytidine/metabolism; Drosophila melanogaster/enzymology; Humans; Hydrogen Bonding; Models, Molecular; Molecular Sequence Data; Phosphotransferases (Alcohol Group Acceptor)/chemistry; Protein Conformation; Sequence Alignment; Structure-Activity Relationship; Substrate Specificity}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{616--620}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Structural Biology}},
  title        = {{Structural basis for substrate specificities of cellular deoxyribonucleoside kinases}},
  url          = {{http://dx.doi.org/10.1038/89661}},
  doi          = {{10.1038/89661}},
  volume       = {{8}},
  year         = {{2001}},
}