A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1

The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition, activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1 replication in human myeloid cells. We describe he...

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Detalles Bibliográficos
Autores principales: Arnold, Laurence H., Kunzelmann, Simone, Webb, Martin R., Taylor, Ian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2014
Materias:
Antiviral Agents
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291348/
https://www.ncbi.nlm.nih.gov/pubmed/25331707
http://dx.doi.org/10.1128/AAC.03903-14
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author Arnold, Laurence H.
Kunzelmann, Simone
Webb, Martin R.
Taylor, Ian A.
author_facet Arnold, Laurence H.
Kunzelmann, Simone
Webb, Martin R.
Taylor, Ian A.
author_sort Arnold, Laurence H.
collection PubMed
description The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition, activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1 replication in human myeloid cells. We describe here an enzyme-coupled assay for quantifying the activation, inhibition, and hydrolysis of dNTPs, nucleotide analogues, and nucleotide analogue inhibitors by triphosphohydrolase enzymes. The assay facilitates mechanistic studies of triphosphohydrolase enzymes and the quantification of off-target effects of nucleotide-based antiviral and chemotherapeutic agents.
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spelling pubmed-42913482015-01-15 A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1 Arnold, Laurence H. Kunzelmann, Simone Webb, Martin R. Taylor, Ian A. Antimicrob Agents Chemother Antiviral Agents The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition, activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1 replication in human myeloid cells. We describe here an enzyme-coupled assay for quantifying the activation, inhibition, and hydrolysis of dNTPs, nucleotide analogues, and nucleotide analogue inhibitors by triphosphohydrolase enzymes. The assay facilitates mechanistic studies of triphosphohydrolase enzymes and the quantification of off-target effects of nucleotide-based antiviral and chemotherapeutic agents. American Society for Microbiology 2014-12-23 2015-01 /pmc/articles/PMC4291348/ /pubmed/25331707 http://dx.doi.org/10.1128/AAC.03903-14 Text en Copyright © 2015, Arnold et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Antiviral Agents
Arnold, Laurence H.
Kunzelmann, Simone
Webb, Martin R.
Taylor, Ian A.
A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title_full A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title_fullStr A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title_full_unstemmed A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title_short A Continuous Enzyme-Coupled Assay for Triphosphohydrolase Activity of HIV-1 Restriction Factor SAMHD1
title_sort continuous enzyme-coupled assay for triphosphohydrolase activity of hiv-1 restriction factor samhd1
topic Antiviral Agents
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291348/
https://www.ncbi.nlm.nih.gov/pubmed/25331707
http://dx.doi.org/10.1128/AAC.03903-14
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