Human and viral nucleoside/nucleotide kinases involved in antiviral drug activation: Structural and catalytic properties

Deville‐Bonne, Dominique; Amri, Chahrazade El; Meyer, Philippe; Chen, Yuxing; Agrofoglio, Luigi A.; Janin, Joël

doi:10.1016/j.antiviral.2010.02.001

Cited by 102 publications

(104 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2.7.4.6) catalyzes the transfer of the γ-phosphate of a donor (ATP or GTP) onto an acceptor (nucleoside or deoxynucleoside diphosphate). The mechanism of catalysis goes through a ping-pong mechanism, where the NDK implicates a covalent intermediate in which a catalytic histidine residue is transiently phosphorylated Garces & Cleland 1969;Deville-Bonne et al 2010). NDK is considered the main source of the dNTP's pool for the DNA polymerase; and for CTP and UTP required by RNA polymerase for transcription (Bilitou et al 2009;DevilleBonne et al 2010).…”

Section: Introductionmentioning

confidence: 97%

Shrimp oncoprotein nm23 is a functional nucleoside diphosphate kinase

Quintero-Reyes

García-Orozco

Sugich-Miranda

et al. 2012

J Bioenerg Biomembr

View full text Add to dashboard Cite

Biosynthesis of nucleoside triphosphates is critical for bioenergetics and nucleic acid replication, and this is achieved by nucleoside diphosphate kinase (NDK). As an emerging biological model and the global importance of shrimp culture, we have addressed the study of the Pacific whiteleg shrimp (Litopenaeus vannamei) NDK. We demonstrated its activity and affinity towards deoxynucleoside diphosphates. Also, the quaternary structure obtained by gel filtration chromatography showed that shrimp NDK is a trimer. Affinity was in the micro-molar range for dADP, dGDP, dTDP and except for dCDP, which presented no detectable interaction by isothermal titration calorimetry, as described previously for Plasmodium falciparum NDK. This information is particularly important, as this enzyme could be used to test nucleotide analogs that can block white spot syndrome virus (WSSV) viral replication and to study its bioenergetics role during hypoxia and fasting.

show abstract

Section: Introductionmentioning

confidence: 97%

Shrimp oncoprotein nm23 is a functional nucleoside diphosphate kinase

Quintero-Reyes

García-Orozco

Sugich-Miranda

et al. 2012

J Bioenerg Biomembr

View full text Add to dashboard Cite

show abstract

“…NDKs are known to have relaxed substrate specificity, since they phosphorylate both deoxyribonucleotides and ribonucleotides (Bilitou et al, 2009;Deville-Bonne et al, 2010). This enzyme has been characterized from several prokaryotic and eukaryotic sources, and has been described as an important housekeeping enzyme that maintains and controls the pool of intracellular nucleotides (Bernard et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates

et al. 2014

View full text Add to dashboard Cite

Nucleoside diphosphate kinase (NDK; EC 2.7.4.6) is an enzyme that catalyzes the third phosphorylation of nucleoside diphosphates, leading to nucleoside triphosphates for DNA replication. Expression of the NDK from Litopenaeus vannamei (LvNDK) is known to be regulated under viral infection. Also, as determined by isothermal titration calorimetry, LvNDK binds both purine and pyrimidine deoxynucleoside diphosphates with high binding affinity for dGDP and dADP and with no heat of binding interaction for dCDP [Quintero-Reyes et al. (2012), J. Bioenerg. Biomembr. 44,[325][326][327][328][329][330][331]. In order to investigate the differences in selectivity, LvNDK was crystallized as binary complexes with both acceptor (dADP and dCDP) and donor (ADP) phosphate-group nucleoside diphosphate substrates and their structures were determined. The three structures with purine or pyrimidine nucleotide ligands are all hexameric. Also, the binding of deoxy or ribonucleotides is similar, as in the former a water molecule replaces the hydrogen bond made by Lys11 to the 2 0 -hydroxyl group of the ribose moiety. This allows Lys11 to maintain a catalytically favourable conformation independently of the kind of sugar found in the nucleotide. Because of this, shrimp NDK may phosphorylate nucleotide analogues to inhibit the viral infections that attack this organism.

show abstract

“…Monophosphorylation is carried out by nucleoside kinases (NKs), diphosphorylation by nucleoside monophosphate kinases (NMPKs), and triphosphorylation by nucleoside diphosphate kinase (NDPK) (Arnér and Eriksson, 1995;Parks and Agarwal, 1973;Kreimeyer et al, 2001;Eriksson et al, 2002;Pasti et al, 2003). These phosphorylation steps are also critical in the activation of all biomedically relevant nucleoside analog prodrugs (Galmarini et al, 2001;Deville-Bonne et al, 2010). Three members of the family of human multidrug resistance-associated proteins (MRP4/5/8) are able to transport nucleoside monophosphate analogs out of cells against concentration gradients.…”

Section: Introductionmentioning

confidence: 99%

Cellular Influx, Efflux, and Anabolism of 3-Carboranyl Thymidine Analogs: Potential Boron Delivery Agents for Neutron Capture Therapy

Sjuvarsson

Damaraju

Mowles

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

3-[5-{2-(2,3-Dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH) is a first generation 3-carboranyl thymidine analog (3CTA) that has been intensively studied as a boron-10 ( 10 B) delivery agent for neutron capture therapy (NCT). N5-2OH is an excellent substrate of thymidine kinase 1 and its favorable biodistribution profile in rodents led to successful preclinical NCT of rats bearing intracerebral RG2 glioma. The present study explored cellular influx and efflux mechanisms of N5-2OH, as well as its intracellular anabolism beyond the monophosphate level. N5-2OH entered cultured human CCRF-CEM cells via passive diffusion, whereas the multidrug resistance-associated protein 4 appeared to be a major mediator of N5-2OH monophosphate efflux. N5-2OH was effectively monophosphorylated in cultured murine L929 [thymidine kinase 1 (TK1 1 )] cells whereas formation of N5-2OH monophosphate was markedly lower in L929 (TK1 -) cell variants. Further metabolism to the di-and triphosphate forms was not observed in any of the cell lines. Regardless of monophosphorylation, parental N5-2OH was the major intracellular component in both TK11 and TK1 -cells. Phosphate transfer experiments with enzyme preparations showed that N5-2OH monophosphate, as well as the monophosphate of a second 3-carboranyl thymidine analog [3-[5-(o-carboran-1-yl)pentan-1-yl]thymidine (N5)], were not substrates of thymidine monophosphate kinase. Surprisingly, N5-diphosphate was phosphorylated by nucleoside diphosphate kinase although N5-triphosphate apparently was not a substrate of DNA polymerase. Our results provide valuable information on the cellular metabolism and pharmacokinetic profile of 3-carboranyl thymidine analogs.

show abstract

Human and viral nucleoside/nucleotide kinases involved in antiviral drug activation: Structural and catalytic properties

Cited by 102 publications

References 187 publications

Shrimp oncoprotein nm23 is a functional nucleoside diphosphate kinase

Shrimp oncoprotein nm23 is a functional nucleoside diphosphate kinase

Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates

Cellular Influx, Efflux, and Anabolism of 3-Carboranyl Thymidine Analogs: Potential Boron Delivery Agents for Neutron Capture Therapy

Contact Info

Product

Resources

About