Characterization of quercetin binding site on DNA gyrase
Gyrases are DNA topology modifying enzymes present only in prokaryotes which makes them an attractive target for antibacterial drugs. Quercetin, one of the most abundant natural flavonoids, inhibits supercoiling activity of bacterial gyrase and induces DNA cleavage. It has been generally assumed tha...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2003-06, Vol.306 (2), p.530-536 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Plaper, Andreja Golob, Mojca Hafner, Iva Oblak, Marko Šolmajer, Tomaž Jerala, Roman |
| description | Gyrases are DNA topology modifying enzymes present only in prokaryotes which makes them an attractive target for antibacterial drugs. Quercetin, one of the most abundant natural flavonoids, inhibits supercoiling activity of bacterial gyrase and induces DNA cleavage. It has been generally assumed that the mechanism of flavonoid inhibition is based on interaction with DNA. We show that quercetin binds to the 24
kDa fragment of gyrase B of
Escherichia coli with a
K
D value of 15
μM and inhibits ATPase activity of gyrase B. Its binding site overlaps with ATP binding pocket and could be competitively replaced by either ATP or novobiocin. The structural model of quercetin–gyrase complex was prepared, based on the close similarity with ATP and quercetin binding sites of the src family tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two different mechanisms based either on interaction with DNA or with ATP binding site of gyrase. |
| doi_str_mv | 10.1016/S0006-291X(03)01006-4 |
| format | Article |
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kDa fragment of gyrase B of
Escherichia coli with a
K
D value of 15
μM and inhibits ATPase activity of gyrase B. Its binding site overlaps with ATP binding pocket and could be competitively replaced by either ATP or novobiocin. The structural model of quercetin–gyrase complex was prepared, based on the close similarity with ATP and quercetin binding sites of the src family tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two different mechanisms based either on interaction with DNA or with ATP binding site of gyrase.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(03)01006-4</identifier><identifier>PMID: 12804597</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenosine Triphosphatases - chemistry ; Adenosine Triphosphate - chemistry ; Adenosine Triphosphate - pharmacology ; ATP binding site ; Binding Sites ; DNA gyrase ; DNA Gyrase - chemistry ; Dose-Response Relationship, Drug ; Escherichia coli - enzymology ; Flavonoids ; Flavonoids - chemistry ; Fluorescence ; Kinetics ; Mechanism of DNA gyrase inhibition ; Models, Molecular ; Molecular model ; Novobiocin - pharmacology ; Protein Binding ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases - chemistry ; Proto-Oncogene Proteins - chemistry ; Proto-Oncogene Proteins c-hck ; Quercetin - chemistry ; Spectrometry, Fluorescence ; Time Factors</subject><ispartof>Biochemical and biophysical research communications, 2003-06, Vol.306 (2), p.530-536</ispartof><rights>2003 Elsevier Science (USA)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-586f92b5ca1783e2d47e4edebfeb151c052d64b3740070616e74e382fc7447ba3</citedby><cites>FETCH-LOGICAL-c510t-586f92b5ca1783e2d47e4edebfeb151c052d64b3740070616e74e382fc7447ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X03010064$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12804597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Plaper, Andreja</creatorcontrib><creatorcontrib>Golob, Mojca</creatorcontrib><creatorcontrib>Hafner, Iva</creatorcontrib><creatorcontrib>Oblak, Marko</creatorcontrib><creatorcontrib>Šolmajer, Tomaž</creatorcontrib><creatorcontrib>Jerala, Roman</creatorcontrib><title>Characterization of quercetin binding site on DNA gyrase</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Gyrases are DNA topology modifying enzymes present only in prokaryotes which makes them an attractive target for antibacterial drugs. Quercetin, one of the most abundant natural flavonoids, inhibits supercoiling activity of bacterial gyrase and induces DNA cleavage. It has been generally assumed that the mechanism of flavonoid inhibition is based on interaction with DNA. We show that quercetin binds to the 24
kDa fragment of gyrase B of
Escherichia coli with a
K
D value of 15
μM and inhibits ATPase activity of gyrase B. Its binding site overlaps with ATP binding pocket and could be competitively replaced by either ATP or novobiocin. The structural model of quercetin–gyrase complex was prepared, based on the close similarity with ATP and quercetin binding sites of the src family tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two different mechanisms based either on interaction with DNA or with ATP binding site of gyrase.</description><subject>Adenosine Triphosphatases - chemistry</subject><subject>Adenosine Triphosphate - chemistry</subject><subject>Adenosine Triphosphate - pharmacology</subject><subject>ATP binding site</subject><subject>Binding Sites</subject><subject>DNA gyrase</subject><subject>DNA Gyrase - chemistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>Escherichia coli - enzymology</subject><subject>Flavonoids</subject><subject>Flavonoids - chemistry</subject><subject>Fluorescence</subject><subject>Kinetics</subject><subject>Mechanism of DNA gyrase inhibition</subject><subject>Models, Molecular</subject><subject>Molecular model</subject><subject>Novobiocin - pharmacology</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Protein-Tyrosine Kinases - chemistry</subject><subject>Proto-Oncogene Proteins - chemistry</subject><subject>Proto-Oncogene Proteins c-hck</subject><subject>Quercetin - chemistry</subject><subject>Spectrometry, Fluorescence</subject><subject>Time Factors</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PwzAMhiMEYuPjJ4B6QnAo2EnatCc0jU9pggMgcYvS1B1BWzuSDmn8eroPwXEny_Lz2tbD2AnCJQKmVy8AkMY8x_dzEBeAy07usD5CDjFHkLus_4f02EEInwCIMs33WQ95BjLJVZ9lww_jjW3Jux_TuqaOmir6mpO31Lo6KlxdunocBddS1A1vngbReOFNoCO2V5lJoONNPWRvd7evw4d49Hz_OByMYpsgtHGSpVXOi8QaVJkgXkpFkkoqKiowQQsJL1NZCCUBFKSYkpIkMl5ZJaUqjDhkZ-u9M990f4VWT12wNJmYmpp50EoIBYKrrSBmKhdS8A5M1qD1TQieKj3zbmr8QiPopVu9cquX4jQIvXKrZZc73RyYF1Mq_1MbmR1wvQao8_HtyOtgHdWWSufJtrps3JYTv24vh4I</recordid><startdate>20030627</startdate><enddate>20030627</enddate><creator>Plaper, Andreja</creator><creator>Golob, Mojca</creator><creator>Hafner, Iva</creator><creator>Oblak, Marko</creator><creator>Šolmajer, Tomaž</creator><creator>Jerala, Roman</creator><general>Elsevier Inc</general><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>7QL</scope><scope>7TM</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20030627</creationdate><title>Characterization of quercetin binding site on DNA gyrase</title><author>Plaper, Andreja ; Golob, Mojca ; Hafner, Iva ; Oblak, Marko ; Šolmajer, Tomaž ; Jerala, Roman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-586f92b5ca1783e2d47e4edebfeb151c052d64b3740070616e74e382fc7447ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adenosine Triphosphatases - chemistry</topic><topic>Adenosine Triphosphate - chemistry</topic><topic>Adenosine Triphosphate - pharmacology</topic><topic>ATP binding site</topic><topic>Binding Sites</topic><topic>DNA gyrase</topic><topic>DNA Gyrase - chemistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>Escherichia coli - enzymology</topic><topic>Flavonoids</topic><topic>Flavonoids - chemistry</topic><topic>Fluorescence</topic><topic>Kinetics</topic><topic>Mechanism of DNA gyrase inhibition</topic><topic>Models, Molecular</topic><topic>Molecular model</topic><topic>Novobiocin - pharmacology</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Protein-Tyrosine Kinases - chemistry</topic><topic>Proto-Oncogene Proteins - chemistry</topic><topic>Proto-Oncogene Proteins c-hck</topic><topic>Quercetin - chemistry</topic><topic>Spectrometry, Fluorescence</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Plaper, Andreja</creatorcontrib><creatorcontrib>Golob, Mojca</creatorcontrib><creatorcontrib>Hafner, Iva</creatorcontrib><creatorcontrib>Oblak, Marko</creatorcontrib><creatorcontrib>Šolmajer, Tomaž</creatorcontrib><creatorcontrib>Jerala, Roman</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nucleic Acids Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Plaper, Andreja</au><au>Golob, Mojca</au><au>Hafner, Iva</au><au>Oblak, Marko</au><au>Šolmajer, Tomaž</au><au>Jerala, Roman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of quercetin binding site on DNA gyrase</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2003-06-27</date><risdate>2003</risdate><volume>306</volume><issue>2</issue><spage>530</spage><epage>536</epage><pages>530-536</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Gyrases are DNA topology modifying enzymes present only in prokaryotes which makes them an attractive target for antibacterial drugs. Quercetin, one of the most abundant natural flavonoids, inhibits supercoiling activity of bacterial gyrase and induces DNA cleavage. It has been generally assumed that the mechanism of flavonoid inhibition is based on interaction with DNA. We show that quercetin binds to the 24
kDa fragment of gyrase B of
Escherichia coli with a
K
D value of 15
μM and inhibits ATPase activity of gyrase B. Its binding site overlaps with ATP binding pocket and could be competitively replaced by either ATP or novobiocin. The structural model of quercetin–gyrase complex was prepared, based on the close similarity with ATP and quercetin binding sites of the src family tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two different mechanisms based either on interaction with DNA or with ATP binding site of gyrase.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12804597</pmid><doi>10.1016/S0006-291X(03)01006-4</doi><tpages>7</tpages></addata></record> |
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| subjects | Adenosine Triphosphatases - chemistry Adenosine Triphosphate - chemistry Adenosine Triphosphate - pharmacology ATP binding site Binding Sites DNA gyrase DNA Gyrase - chemistry Dose-Response Relationship, Drug Escherichia coli - enzymology Flavonoids Flavonoids - chemistry Fluorescence Kinetics Mechanism of DNA gyrase inhibition Models, Molecular Molecular model Novobiocin - pharmacology Protein Binding Protein Structure, Tertiary Protein-Tyrosine Kinases - chemistry Proto-Oncogene Proteins - chemistry Proto-Oncogene Proteins c-hck Quercetin - chemistry Spectrometry, Fluorescence Time Factors |
| title | Characterization of quercetin binding site on DNA gyrase |
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