2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase
•2,3-Dihydroxy-quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase.•2,3-Dihydroxy-quinoxaline promotes ATPase activity of herpesvirus thymidine kinase.•This promotion is dose-dependent and follows the Michaelis–Menten scheme.•We propose a kinetic scheme for the whole proce...
Gespeichert in:
| Veröffentlicht in: | FEBS letters 2014-01, Vol.588 (3), p.509-511 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 511 |
|---|---|
| container_issue | 3 |
| container_start_page | 509 |
| container_title | FEBS letters |
| container_volume | 588 |
| creator | Zeifman, Alexey A. Novikov, Fedor N. Stroylov, Victor S. Stroganov, Oleg V. Chilov, Ghermes G. Skoblov, Alexander Y. Miroshnikov, Anatoly I. Skoblov, Yuri S. |
| description | •2,3-Dihydroxy-quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase.•2,3-Dihydroxy-quinoxaline promotes ATPase activity of herpesvirus thymidine kinase.•This promotion is dose-dependent and follows the Michaelis–Menten scheme.•We propose a kinetic scheme for the whole process that is consistent with the experimental data.
2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki=250μM (95% CI: 106–405μM) and dose-dependently increased the rate of the ATP hydrolysis with KM=112μM (95% CI: 28–195μM). The kinetic scheme consistent with this experimental data is proposed. |
| doi_str_mv | 10.1016/j.febslet.2013.12.017 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1668262419</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014579313009253</els_id><sourcerecordid>1668262419</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5103-d26c73ba5bf674efe6519836195c5402d6c0c4105b932fef4839bb60c9972aa93</originalsourceid><addsrcrecordid>eNqNkc1u1DAURi0EotPCI4CyZEFSX9tx4hUqpWUqVWqlFhZsLMe5UT3kZ2onZfL2dTQDW7qyLJ_v89U9hHwAmgEFebrJGqxCi2PGKPAMWEaheEVWUBY85UKWr8mKUhBpXih-RI5D2NB4L0G9JUdM8EJwASvyi33m6Tf3MNd-2M3p4-T6YWda12Pi-nqyGJKz-1sTMDF2dE9unJOhSdbot_HlznXbFnfJT-enkIwPc-fqJfnb9THxjrxpTBvw_eE8IT8uL-7P1-n1zfer87Pr1OZAeVozaQtembxqZCGwQZmDKrkEldtcUFZLS60AmleKswYbUXJVVZJapQpmjOIn5NO-d-uHxwnDqDsXLLat6XGYggYpSyaZgBegQrECZAksovketX4IwWOjt951xs8aqF4M6I0-GNCLAQ1MRwMx9_HwxVR1WP9L_V15BNZ74I9rcX5Zq768-MruFp2LTeCUKpbzWPVlX4VxvU8OvQ7WYW-xdh7tqOvB_WfaZ3U2rl8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1492716812</pqid></control><display><type>article</type><title>2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>ScienceDirect Journals (5 years ago - present)</source><source>Alma/SFX Local Collection</source><creator>Zeifman, Alexey A. ; Novikov, Fedor N. ; Stroylov, Victor S. ; Stroganov, Oleg V. ; Chilov, Ghermes G. ; Skoblov, Alexander Y. ; Miroshnikov, Anatoly I. ; Skoblov, Yuri S.</creator><creatorcontrib>Zeifman, Alexey A. ; Novikov, Fedor N. ; Stroylov, Victor S. ; Stroganov, Oleg V. ; Chilov, Ghermes G. ; Skoblov, Alexander Y. ; Miroshnikov, Anatoly I. ; Skoblov, Yuri S.</creatorcontrib><description>•2,3-Dihydroxy-quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase.•2,3-Dihydroxy-quinoxaline promotes ATPase activity of herpesvirus thymidine kinase.•This promotion is dose-dependent and follows the Michaelis–Menten scheme.•We propose a kinetic scheme for the whole process that is consistent with the experimental data.
2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki=250μM (95% CI: 106–405μM) and dose-dependently increased the rate of the ATP hydrolysis with KM=112μM (95% CI: 28–195μM). The kinetic scheme consistent with this experimental data is proposed.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2013.12.017</identifier><identifier>PMID: 24374341</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>2,3-dihydroxy-quinoxaline ; Acyclovir - therapeutic use ; Adenosine Triphosphatases - chemistry ; Catalysis ; DHQ ; Enzyme kinetic ; Herpes simplex virus ; Herpes Simplex Virus thymidine kinase ; HSV-TK ; Humans ; Inhibition ; Kinetics ; Molecular docking ; Phosphorylation - drug effects ; Quinoxalines - pharmacology ; Simplexvirus - drug effects ; Simplexvirus - enzymology ; thin layer chromatography ; Thymidine kinase ; Thymidine Kinase - antagonists & inhibitors ; Thymidine Kinase - chemistry ; TLC</subject><ispartof>FEBS letters, 2014-01, Vol.588 (3), p.509-511</ispartof><rights>2013 Federation of European Biochemical Societies</rights><rights>FEBS Letters 588 (2014) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5103-d26c73ba5bf674efe6519836195c5402d6c0c4105b932fef4839bb60c9972aa93</citedby><cites>FETCH-LOGICAL-c5103-d26c73ba5bf674efe6519836195c5402d6c0c4105b932fef4839bb60c9972aa93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.febslet.2013.12.017$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.febslet.2013.12.017$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,1433,3550,27924,27925,45574,45575,45995,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24374341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeifman, Alexey A.</creatorcontrib><creatorcontrib>Novikov, Fedor N.</creatorcontrib><creatorcontrib>Stroylov, Victor S.</creatorcontrib><creatorcontrib>Stroganov, Oleg V.</creatorcontrib><creatorcontrib>Chilov, Ghermes G.</creatorcontrib><creatorcontrib>Skoblov, Alexander Y.</creatorcontrib><creatorcontrib>Miroshnikov, Anatoly I.</creatorcontrib><creatorcontrib>Skoblov, Yuri S.</creatorcontrib><title>2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>•2,3-Dihydroxy-quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase.•2,3-Dihydroxy-quinoxaline promotes ATPase activity of herpesvirus thymidine kinase.•This promotion is dose-dependent and follows the Michaelis–Menten scheme.•We propose a kinetic scheme for the whole process that is consistent with the experimental data.
2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki=250μM (95% CI: 106–405μM) and dose-dependently increased the rate of the ATP hydrolysis with KM=112μM (95% CI: 28–195μM). The kinetic scheme consistent with this experimental data is proposed.</description><subject>2,3-dihydroxy-quinoxaline</subject><subject>Acyclovir - therapeutic use</subject><subject>Adenosine Triphosphatases - chemistry</subject><subject>Catalysis</subject><subject>DHQ</subject><subject>Enzyme kinetic</subject><subject>Herpes simplex virus</subject><subject>Herpes Simplex Virus thymidine kinase</subject><subject>HSV-TK</subject><subject>Humans</subject><subject>Inhibition</subject><subject>Kinetics</subject><subject>Molecular docking</subject><subject>Phosphorylation - drug effects</subject><subject>Quinoxalines - pharmacology</subject><subject>Simplexvirus - drug effects</subject><subject>Simplexvirus - enzymology</subject><subject>thin layer chromatography</subject><subject>Thymidine kinase</subject><subject>Thymidine Kinase - antagonists & inhibitors</subject><subject>Thymidine Kinase - chemistry</subject><subject>TLC</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAURi0EotPCI4CyZEFSX9tx4hUqpWUqVWqlFhZsLMe5UT3kZ2onZfL2dTQDW7qyLJ_v89U9hHwAmgEFebrJGqxCi2PGKPAMWEaheEVWUBY85UKWr8mKUhBpXih-RI5D2NB4L0G9JUdM8EJwASvyi33m6Tf3MNd-2M3p4-T6YWda12Pi-nqyGJKz-1sTMDF2dE9unJOhSdbot_HlznXbFnfJT-enkIwPc-fqJfnb9THxjrxpTBvw_eE8IT8uL-7P1-n1zfer87Pr1OZAeVozaQtembxqZCGwQZmDKrkEldtcUFZLS60AmleKswYbUXJVVZJapQpmjOIn5NO-d-uHxwnDqDsXLLat6XGYggYpSyaZgBegQrECZAksovketX4IwWOjt951xs8aqF4M6I0-GNCLAQ1MRwMx9_HwxVR1WP9L_V15BNZ74I9rcX5Zq768-MruFp2LTeCUKpbzWPVlX4VxvU8OvQ7WYW-xdh7tqOvB_WfaZ3U2rl8</recordid><startdate>20140131</startdate><enddate>20140131</enddate><creator>Zeifman, Alexey A.</creator><creator>Novikov, Fedor N.</creator><creator>Stroylov, Victor S.</creator><creator>Stroganov, Oleg V.</creator><creator>Chilov, Ghermes G.</creator><creator>Skoblov, Alexander Y.</creator><creator>Miroshnikov, Anatoly I.</creator><creator>Skoblov, Yuri S.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20140131</creationdate><title>2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase</title><author>Zeifman, Alexey A. ; Novikov, Fedor N. ; Stroylov, Victor S. ; Stroganov, Oleg V. ; Chilov, Ghermes G. ; Skoblov, Alexander Y. ; Miroshnikov, Anatoly I. ; Skoblov, Yuri S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5103-d26c73ba5bf674efe6519836195c5402d6c0c4105b932fef4839bb60c9972aa93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>2,3-dihydroxy-quinoxaline</topic><topic>Acyclovir - therapeutic use</topic><topic>Adenosine Triphosphatases - chemistry</topic><topic>Catalysis</topic><topic>DHQ</topic><topic>Enzyme kinetic</topic><topic>Herpes simplex virus</topic><topic>Herpes Simplex Virus thymidine kinase</topic><topic>HSV-TK</topic><topic>Humans</topic><topic>Inhibition</topic><topic>Kinetics</topic><topic>Molecular docking</topic><topic>Phosphorylation - drug effects</topic><topic>Quinoxalines - pharmacology</topic><topic>Simplexvirus - drug effects</topic><topic>Simplexvirus - enzymology</topic><topic>thin layer chromatography</topic><topic>Thymidine kinase</topic><topic>Thymidine Kinase - antagonists & inhibitors</topic><topic>Thymidine Kinase - chemistry</topic><topic>TLC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeifman, Alexey A.</creatorcontrib><creatorcontrib>Novikov, Fedor N.</creatorcontrib><creatorcontrib>Stroylov, Victor S.</creatorcontrib><creatorcontrib>Stroganov, Oleg V.</creatorcontrib><creatorcontrib>Chilov, Ghermes G.</creatorcontrib><creatorcontrib>Skoblov, Alexander Y.</creatorcontrib><creatorcontrib>Miroshnikov, Anatoly I.</creatorcontrib><creatorcontrib>Skoblov, Yuri S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeifman, Alexey A.</au><au>Novikov, Fedor N.</au><au>Stroylov, Victor S.</au><au>Stroganov, Oleg V.</au><au>Chilov, Ghermes G.</au><au>Skoblov, Alexander Y.</au><au>Miroshnikov, Anatoly I.</au><au>Skoblov, Yuri S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2014-01-31</date><risdate>2014</risdate><volume>588</volume><issue>3</issue><spage>509</spage><epage>511</epage><pages>509-511</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>•2,3-Dihydroxy-quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase.•2,3-Dihydroxy-quinoxaline promotes ATPase activity of herpesvirus thymidine kinase.•This promotion is dose-dependent and follows the Michaelis–Menten scheme.•We propose a kinetic scheme for the whole process that is consistent with the experimental data.
2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki=250μM (95% CI: 106–405μM) and dose-dependently increased the rate of the ATP hydrolysis with KM=112μM (95% CI: 28–195μM). The kinetic scheme consistent with this experimental data is proposed.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>24374341</pmid><doi>10.1016/j.febslet.2013.12.017</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 2014-01, Vol.588 (3), p.509-511 |
| issn | 0014-5793 1873-3468 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1668262419 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; ScienceDirect Journals (5 years ago - present); Alma/SFX Local Collection |
| subjects | 2,3-dihydroxy-quinoxaline Acyclovir - therapeutic use Adenosine Triphosphatases - chemistry Catalysis DHQ Enzyme kinetic Herpes simplex virus Herpes Simplex Virus thymidine kinase HSV-TK Humans Inhibition Kinetics Molecular docking Phosphorylation - drug effects Quinoxalines - pharmacology Simplexvirus - drug effects Simplexvirus - enzymology thin layer chromatography Thymidine kinase Thymidine Kinase - antagonists & inhibitors Thymidine Kinase - chemistry TLC |
| title | 2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T22%3A37%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=2,3-Dihydroxy-quinoxaline%20induces%20ATPase%20activity%20of%20Herpes%20Simplex%20Virus%20thymidine%20kinase&rft.jtitle=FEBS%20letters&rft.au=Zeifman,%20Alexey%20A.&rft.date=2014-01-31&rft.volume=588&rft.issue=3&rft.spage=509&rft.epage=511&rft.pages=509-511&rft.issn=0014-5793&rft.eissn=1873-3468&rft_id=info:doi/10.1016/j.febslet.2013.12.017&rft_dat=%3Cproquest_cross%3E1668262419%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1492716812&rft_id=info:pmid/24374341&rft_els_id=S0014579313009253&rfr_iscdi=true |