Rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNA polymerase active center
Rifamycin antibacterial agents inhibit bacterial RNA polymerase (RNAP) by binding to a site adjacent to the RNAP active center and preventing synthesis of RNA products >2-3 nt in length. Recently, Artsimovitch et al. [(2005) Cell 122:351-363] proposed that rifamycins function by allosteric modula...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-09, Vol.105 (39), p.14820-14825 |
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| container_issue | 39 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Feklistov, Andrey Mekler, Vladimir Jiang, Qiaorong Westblade, Lars F Irschik, Herbert Jansen, Rolf Mustaev, Arkady Darst, Seth A Ebright, Richard H |
| description | Rifamycin antibacterial agents inhibit bacterial RNA polymerase (RNAP) by binding to a site adjacent to the RNAP active center and preventing synthesis of RNA products >2-3 nt in length. Recently, Artsimovitch et al. [(2005) Cell 122:351-363] proposed that rifamycins function by allosteric modulation of binding of Mg²⁺ to the RNAP active center and presented three lines of biochemical evidence consistent with this proposal. Here, we show that rifamycins do not affect the affinity of binding of Mg²⁺ to the RNAP active center, and we reassess the three lines of biochemical evidence, obtaining results not supportive of the proposal. We conclude that rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNAP active center. |
| doi_str_mv | 10.1073/pnas.0802822105 |
| format | Article |
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Recently, Artsimovitch et al. [(2005) Cell 122:351-363] proposed that rifamycins function by allosteric modulation of binding of Mg²⁺ to the RNAP active center and presented three lines of biochemical evidence consistent with this proposal. Here, we show that rifamycins do not affect the affinity of binding of Mg²⁺ to the RNAP active center, and we reassess the three lines of biochemical evidence, obtaining results not supportive of the proposal. We conclude that rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNAP active center.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0802822105</identifier><identifier>PMID: 18787125</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Allosteric Regulation - drug effects ; Anti-Bacterial Agents - pharmacology ; Antibacterials ; Binding sites ; Binding Sites - drug effects ; Biochemical mechanisms ; Biochemistry ; Biological Sciences ; Crystal structure ; DNA-Directed RNA Polymerases - antagonists & inhibitors ; DNA-Directed RNA Polymerases - genetics ; DNA-Directed RNA Polymerases - metabolism ; Experiment design ; Genetic mutation ; Magnesium - metabolism ; Mutation ; Plasmids ; Rifamycins ; Rifamycins - pharmacology ; RNA</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-09, Vol.105 (39), p.14820-14825</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/39.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25464319$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25464319$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18787125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feklistov, Andrey</creatorcontrib><creatorcontrib>Mekler, Vladimir</creatorcontrib><creatorcontrib>Jiang, Qiaorong</creatorcontrib><creatorcontrib>Westblade, Lars F</creatorcontrib><creatorcontrib>Irschik, Herbert</creatorcontrib><creatorcontrib>Jansen, Rolf</creatorcontrib><creatorcontrib>Mustaev, Arkady</creatorcontrib><creatorcontrib>Darst, Seth A</creatorcontrib><creatorcontrib>Ebright, Richard H</creatorcontrib><title>Rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNA polymerase active center</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Rifamycin antibacterial agents inhibit bacterial RNA polymerase (RNAP) by binding to a site adjacent to the RNAP active center and preventing synthesis of RNA products >2-3 nt in length. 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We conclude that rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNAP active center.</description><subject>Allosteric Regulation - drug effects</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterials</subject><subject>Binding sites</subject><subject>Binding Sites - drug effects</subject><subject>Biochemical mechanisms</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Crystal structure</subject><subject>DNA-Directed RNA Polymerases - antagonists & inhibitors</subject><subject>DNA-Directed RNA Polymerases - genetics</subject><subject>DNA-Directed RNA Polymerases - metabolism</subject><subject>Experiment design</subject><subject>Genetic mutation</subject><subject>Magnesium - metabolism</subject><subject>Mutation</subject><subject>Plasmids</subject><subject>Rifamycins</subject><subject>Rifamycins - pharmacology</subject><subject>RNA</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9vFCEYh4nR2G317EnlZOJh6wsDDFxMmsZ_SdWk2jNhZmBLw8B2YBr32K_k0aMfxU8iddeqJ0_w5nny--UFhB4ROCTQNi_W0eRDkEAlpQT4HbQgoMhSMAV30QKAtkvJKNtD-zlfAIDiEu6jPSJb2RLKF2g89c6Mm97HjIeEYyrYzbEvPkXcbbAJIeViJ9_jMQ1zML9AcrjzcfBxdXN9v_r-9cf1N1wSLucWn344wusUNqOdTLbY1Kwri3sba8wDdM-ZkO3D3XmAzl6_-nz8dnny8c2746OTpaNKlWVnBKeUdVS5XjIpmWMtF91ALNQlOVVQR9bzOinqKKiWEEmIJWIwjHNoDtDLbe567kY73JRPJuj15EczbXQyXv9Loj_Xq3SlKRct46QGPNsFTOlytrno0efehmCiTXPWQgnaiKap4pO_m24rfr9wFZ7vhPpVfzBw3ShNmKSg3RxCsV9KdfF_3Ko83ioXuaTp1qGcCdYQVfnTLXcmabOafNZnnyiQBghnrRC8-Qk8e6si</recordid><startdate>20080930</startdate><enddate>20080930</enddate><creator>Feklistov, Andrey</creator><creator>Mekler, Vladimir</creator><creator>Jiang, Qiaorong</creator><creator>Westblade, Lars F</creator><creator>Irschik, Herbert</creator><creator>Jansen, Rolf</creator><creator>Mustaev, Arkady</creator><creator>Darst, Seth A</creator><creator>Ebright, Richard H</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080930</creationdate><title>Rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNA polymerase active center</title><author>Feklistov, Andrey ; Mekler, Vladimir ; Jiang, Qiaorong ; Westblade, Lars F ; Irschik, Herbert ; Jansen, Rolf ; Mustaev, Arkady ; Darst, Seth A ; Ebright, Richard H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f299t-ba65224b29fc84884f4756bd1e010552907564c501092f209711811e16da45503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Allosteric Regulation - drug effects</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibacterials</topic><topic>Binding sites</topic><topic>Binding Sites - drug effects</topic><topic>Biochemical mechanisms</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Crystal structure</topic><topic>DNA-Directed RNA Polymerases - antagonists & inhibitors</topic><topic>DNA-Directed RNA Polymerases - genetics</topic><topic>DNA-Directed RNA Polymerases - metabolism</topic><topic>Experiment design</topic><topic>Genetic mutation</topic><topic>Magnesium - metabolism</topic><topic>Mutation</topic><topic>Plasmids</topic><topic>Rifamycins</topic><topic>Rifamycins - pharmacology</topic><topic>RNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feklistov, Andrey</creatorcontrib><creatorcontrib>Mekler, Vladimir</creatorcontrib><creatorcontrib>Jiang, Qiaorong</creatorcontrib><creatorcontrib>Westblade, Lars F</creatorcontrib><creatorcontrib>Irschik, Herbert</creatorcontrib><creatorcontrib>Jansen, Rolf</creatorcontrib><creatorcontrib>Mustaev, Arkady</creatorcontrib><creatorcontrib>Darst, Seth A</creatorcontrib><creatorcontrib>Ebright, Richard H</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feklistov, Andrey</au><au>Mekler, Vladimir</au><au>Jiang, Qiaorong</au><au>Westblade, Lars F</au><au>Irschik, Herbert</au><au>Jansen, Rolf</au><au>Mustaev, Arkady</au><au>Darst, Seth A</au><au>Ebright, Richard H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNA polymerase active center</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2008-09-30</date><risdate>2008</risdate><volume>105</volume><issue>39</issue><spage>14820</spage><epage>14825</epage><pages>14820-14825</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Rifamycin antibacterial agents inhibit bacterial RNA polymerase (RNAP) by binding to a site adjacent to the RNAP active center and preventing synthesis of RNA products >2-3 nt in length. Recently, Artsimovitch et al. [(2005) Cell 122:351-363] proposed that rifamycins function by allosteric modulation of binding of Mg²⁺ to the RNAP active center and presented three lines of biochemical evidence consistent with this proposal. Here, we show that rifamycins do not affect the affinity of binding of Mg²⁺ to the RNAP active center, and we reassess the three lines of biochemical evidence, obtaining results not supportive of the proposal. We conclude that rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNAP active center.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18787125</pmid><doi>10.1073/pnas.0802822105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-09, Vol.105 (39), p.14820-14825 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Allosteric Regulation - drug effects Anti-Bacterial Agents - pharmacology Antibacterials Binding sites Binding Sites - drug effects Biochemical mechanisms Biochemistry Biological Sciences Crystal structure DNA-Directed RNA Polymerases - antagonists & inhibitors DNA-Directed RNA Polymerases - genetics DNA-Directed RNA Polymerases - metabolism Experiment design Genetic mutation Magnesium - metabolism Mutation Plasmids Rifamycins Rifamycins - pharmacology RNA |
| title | Rifamycins do not function by allosteric modulation of binding of Mg²⁺ to the RNA polymerase active center |
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