Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog
Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-speci...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1996-06, Vol.272 (5270), p.1943-1946 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1946 |
|---|---|
| container_issue | 5270 |
| container_start_page | 1943 |
| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 272 |
| creator | Stassinopoulos, Adonis Ji, Jie Gao, Xiaolian Goldberg, Irving H. |
| description | Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode involves major groove recognition by the drug carbohydrate unit and tight fitting of the wedge-shaped drug in the triangular prism pocket formed by the two looped-out bulge bases and the neighboring base pairs. The two drug rings mimic helical DNA bases, complementing the bent DNA structure. The putative abstracting drug radical is 2.2 ± 0.1 angstroms from the pro-S H5′ of the target bulge nucleotide. This structure clarifies the mechanism of bulge recognition and cleavage by a drug and provides insight into the design of bulge-specific nucleic acid binding molecules. |
| doi_str_mv | 10.1126/science.272.5270.1943 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_78135615</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A18480788</galeid><jstor_id>2890625</jstor_id><sourcerecordid>A18480788</sourcerecordid><originalsourceid>FETCH-LOGICAL-c688t-17b14e32b93900d453d4f01507277826f990b8ea75dcd9d519307dc8cacf02433</originalsourceid><addsrcrecordid>eNqN0k9r2zAYBnAzNros2zdYwYyx7VBn-mNZ8jHJuqwQmkPaXYUiv_YcFCmT7LX99lNICGSEUXQQ6PlJIOlJkkuMRhiT4mvQLVgNI8LJiBEeV8ucvkgGGJUsKwmiL5MBQrTIBOLsdfImhDVCMSvpRXIhCiZwIQbJ_dKZvmudTZed73XXe0hdnar07sFlExUg_XY7Tie9aSCdus3WwCNU6UPb_UqVTa8tVO2TjZEB9ae1TTq2yrjmbfKqVibAu8M8TO6_X99Nf2TzxexmOp5nuhCiyzBf4RwoWZW0RKjKGa3yGmGGOOFckKIuS7QSoDirdFVWDJcU8UoLrXSNSE7pMPm0P3fr3e8eQic3bdBgjLLg-iC5wJQVmEX4-f8wpznDgu_kh3_k2vU-3ipIsjssJ_EFh8nVHjXKgGxt7TqvdAMWfLy-hbqNy2Ms8vj2QkSeneFxVLBp9Tn_5cRH0sFj16g-BHmzvH02Xfx8Np3MnkvFbH5Cr85R7YyBBmT87unihLM9196F4KGWW99ulH-SGMldr-Wh1zL2Wu56LXe9jvsuD9_SrzZQHXcdihzzj4dcBa1M7ZXVbTgyigmlBY_s_Z6tQ-f8MSaiRAVh9C9w9gPj</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213564259</pqid></control><display><type>article</type><title>Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>American Association for the Advancement of Science</source><creator>Stassinopoulos, Adonis ; Ji, Jie ; Gao, Xiaolian ; Goldberg, Irving H.</creator><creatorcontrib>Stassinopoulos, Adonis ; Ji, Jie ; Gao, Xiaolian ; Goldberg, Irving H.</creatorcontrib><description>Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode involves major groove recognition by the drug carbohydrate unit and tight fitting of the wedge-shaped drug in the triangular prism pocket formed by the two looped-out bulge bases and the neighboring base pairs. The two drug rings mimic helical DNA bases, complementing the bent DNA structure. The putative abstracting drug radical is 2.2 ± 0.1 angstroms from the pro-S H5′ of the target bulge nucleotide. This structure clarifies the mechanism of bulge recognition and cleavage by a drug and provides insight into the design of bulge-specific nucleic acid binding molecules.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.272.5270.1943</identifier><identifier>PMID: 8658168</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Analytical, structural and metabolic biochemistry ; Antibiotics ; Base Composition ; Base Sequence ; Biochemistry ; Biological and medical sciences ; Chemical bases ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - metabolism ; Dna, deoxyribonucleoproteins ; Enediynes ; Fundamental and applied biological sciences. Psychology ; Geometric Concepts ; Geometry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Molecules ; NMR ; Nuclear magnetic resonance ; Nucleic Acid Conformation ; Nucleic acids ; Oligodeoxyribonucleotides - chemistry ; Oligodeoxyribonucleotides - metabolism ; Pharmaceutical microbiology ; Protons ; Solvents ; Spectroscopy ; Sugars ; Zinostatin - analogs & derivatives ; Zinostatin - chemistry ; Zinostatin - metabolism</subject><ispartof>Science (American Association for the Advancement of Science), 1996-06, Vol.272 (5270), p.1943-1946</ispartof><rights>Copyright 1996 American Association for the Advancement of Science</rights><rights>1996 INIST-CNRS</rights><rights>COPYRIGHT 1996 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1996 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Jun 28, 1996</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c688t-17b14e32b93900d453d4f01507277826f990b8ea75dcd9d519307dc8cacf02433</citedby><cites>FETCH-LOGICAL-c688t-17b14e32b93900d453d4f01507277826f990b8ea75dcd9d519307dc8cacf02433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2890625$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2890625$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3123367$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8658168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stassinopoulos, Adonis</creatorcontrib><creatorcontrib>Ji, Jie</creatorcontrib><creatorcontrib>Gao, Xiaolian</creatorcontrib><creatorcontrib>Goldberg, Irving H.</creatorcontrib><title>Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode involves major groove recognition by the drug carbohydrate unit and tight fitting of the wedge-shaped drug in the triangular prism pocket formed by the two looped-out bulge bases and the neighboring base pairs. The two drug rings mimic helical DNA bases, complementing the bent DNA structure. The putative abstracting drug radical is 2.2 ± 0.1 angstroms from the pro-S H5′ of the target bulge nucleotide. This structure clarifies the mechanism of bulge recognition and cleavage by a drug and provides insight into the design of bulge-specific nucleic acid binding molecules.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antibiotics</subject><subject>Base Composition</subject><subject>Base Sequence</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Chemical bases</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>Dna, deoxyribonucleoproteins</subject><subject>Enediynes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Geometric Concepts</subject><subject>Geometry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Molecules</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleic acids</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Oligodeoxyribonucleotides - metabolism</subject><subject>Pharmaceutical microbiology</subject><subject>Protons</subject><subject>Solvents</subject><subject>Spectroscopy</subject><subject>Sugars</subject><subject>Zinostatin - analogs & derivatives</subject><subject>Zinostatin - chemistry</subject><subject>Zinostatin - metabolism</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0k9r2zAYBnAzNros2zdYwYyx7VBn-mNZ8jHJuqwQmkPaXYUiv_YcFCmT7LX99lNICGSEUXQQ6PlJIOlJkkuMRhiT4mvQLVgNI8LJiBEeV8ucvkgGGJUsKwmiL5MBQrTIBOLsdfImhDVCMSvpRXIhCiZwIQbJ_dKZvmudTZed73XXe0hdnar07sFlExUg_XY7Tie9aSCdus3WwCNU6UPb_UqVTa8tVO2TjZEB9ae1TTq2yrjmbfKqVibAu8M8TO6_X99Nf2TzxexmOp5nuhCiyzBf4RwoWZW0RKjKGa3yGmGGOOFckKIuS7QSoDirdFVWDJcU8UoLrXSNSE7pMPm0P3fr3e8eQic3bdBgjLLg-iC5wJQVmEX4-f8wpznDgu_kh3_k2vU-3ipIsjssJ_EFh8nVHjXKgGxt7TqvdAMWfLy-hbqNy2Ms8vj2QkSeneFxVLBp9Tn_5cRH0sFj16g-BHmzvH02Xfx8Np3MnkvFbH5Cr85R7YyBBmT87unihLM9196F4KGWW99ulH-SGMldr-Wh1zL2Wu56LXe9jvsuD9_SrzZQHXcdihzzj4dcBa1M7ZXVbTgyigmlBY_s_Z6tQ-f8MSaiRAVh9C9w9gPj</recordid><startdate>19960628</startdate><enddate>19960628</enddate><creator>Stassinopoulos, Adonis</creator><creator>Ji, Jie</creator><creator>Gao, Xiaolian</creator><creator>Goldberg, Irving H.</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>IQODW</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>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>0-V</scope><scope>3V.</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9-</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0K</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19960628</creationdate><title>Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog</title><author>Stassinopoulos, Adonis ; Ji, Jie ; Gao, Xiaolian ; Goldberg, Irving H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c688t-17b14e32b93900d453d4f01507277826f990b8ea75dcd9d519307dc8cacf02433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Antibiotics</topic><topic>Base Composition</topic><topic>Base Sequence</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Chemical bases</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>Dna, deoxyribonucleoproteins</topic><topic>Enediynes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Geometric Concepts</topic><topic>Geometry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Molecules</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic acids</topic><topic>Oligodeoxyribonucleotides - chemistry</topic><topic>Oligodeoxyribonucleotides - metabolism</topic><topic>Pharmaceutical microbiology</topic><topic>Protons</topic><topic>Solvents</topic><topic>Spectroscopy</topic><topic>Sugars</topic><topic>Zinostatin - analogs & derivatives</topic><topic>Zinostatin - chemistry</topic><topic>Zinostatin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stassinopoulos, Adonis</creatorcontrib><creatorcontrib>Ji, Jie</creatorcontrib><creatorcontrib>Gao, Xiaolian</creatorcontrib><creatorcontrib>Goldberg, Irving H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>Gale In Context: Biography</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Education Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Education Collection</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Agricultural Science Database</collection><collection>Education Database</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Education</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stassinopoulos, Adonis</au><au>Ji, Jie</au><au>Gao, Xiaolian</au><au>Goldberg, Irving H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1996-06-28</date><risdate>1996</risdate><volume>272</volume><issue>5270</issue><spage>1943</spage><epage>1946</epage><pages>1943-1946</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode involves major groove recognition by the drug carbohydrate unit and tight fitting of the wedge-shaped drug in the triangular prism pocket formed by the two looped-out bulge bases and the neighboring base pairs. The two drug rings mimic helical DNA bases, complementing the bent DNA structure. The putative abstracting drug radical is 2.2 ± 0.1 angstroms from the pro-S H5′ of the target bulge nucleotide. This structure clarifies the mechanism of bulge recognition and cleavage by a drug and provides insight into the design of bulge-specific nucleic acid binding molecules.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>8658168</pmid><doi>10.1126/science.272.5270.1943</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1996-06, Vol.272 (5270), p.1943-1946 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78135615 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | Analytical, structural and metabolic biochemistry Antibiotics Base Composition Base Sequence Biochemistry Biological and medical sciences Chemical bases Deoxyribonucleic acid DNA DNA - chemistry DNA - metabolism Dna, deoxyribonucleoproteins Enediynes Fundamental and applied biological sciences. Psychology Geometric Concepts Geometry Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Molecules NMR Nuclear magnetic resonance Nucleic Acid Conformation Nucleic acids Oligodeoxyribonucleotides - chemistry Oligodeoxyribonucleotides - metabolism Pharmaceutical microbiology Protons Solvents Spectroscopy Sugars Zinostatin - analogs & derivatives Zinostatin - chemistry Zinostatin - metabolism |
| title | Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T13%3A32%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Solution%20Structure%20of%20a%20Two-Base%20DNA%20Bulge%20Complexed%20with%20an%20Enediyne%20Cleaving%20Analog&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Stassinopoulos,%20Adonis&rft.date=1996-06-28&rft.volume=272&rft.issue=5270&rft.spage=1943&rft.epage=1946&rft.pages=1943-1946&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.272.5270.1943&rft_dat=%3Cgale_proqu%3EA18480788%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213564259&rft_id=info:pmid/8658168&rft_galeid=A18480788&rft_jstor_id=2890625&rfr_iscdi=true |