X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry
The 2-deoxy- scyllo -inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine–containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S -adenosyl- l -methioni...
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| Veröffentlicht in: | Proc. Natl. Acad. Sci. USA 2013-10, Vol.110 (40), p.15949-15954 |
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| creator | Goldman, Peter J. Grove, Tyler L. Booker, Squire J. Drennan, Catherine L. |
| description | The 2-deoxy- scyllo -inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine–containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S -adenosyl- l -methionine (AdoMet) radical enzyme. To examine how BtrN employs AdoMet radical chemistry, we have determined its structure with AdoMet and substrate to 1.56 Å resolution. We find a previously undescribed modification to the core AdoMet radical fold: instead of the canonical (β/α) ₆ architecture, BtrN displays a (β ₅/α ₄) motif. We further find that an auxiliary [4Fe-4S] cluster in BtrN, thought to bind substrate, is instead implicated in substrate–radical oxidation. High structural homology in the auxiliary cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofactor biosynthetic enzyme MoaA provides support for the establishment of an AdoMet radical structural motif that is likely common to ∼6,400 uncharacterized AdoMet radical enzymes. |
| doi_str_mv | 10.1073/pnas.1312228110 |
| format | Article |
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(ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><description>The 2-deoxy- scyllo -inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine–containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S -adenosyl- l -methionine (AdoMet) radical enzyme. To examine how BtrN employs AdoMet radical chemistry, we have determined its structure with AdoMet and substrate to 1.56 Å resolution. We find a previously undescribed modification to the core AdoMet radical fold: instead of the canonical (β/α) ₆ architecture, BtrN displays a (β ₅/α ₄) motif. We further find that an auxiliary [4Fe-4S] cluster in BtrN, thought to bind substrate, is instead implicated in substrate–radical oxidation. High structural homology in the auxiliary cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofactor biosynthetic enzyme MoaA provides support for the establishment of an AdoMet radical structural motif that is likely common to ∼6,400 uncharacterized AdoMet radical enzymes.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1312228110</identifier><identifier>PMID: 24048029</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>aminoglycoside antibiotics ; Aminoglycosides ; Bacillus - enzymology ; Bacillus circulans ; Bacteria ; Biochemistry ; Biological Sciences ; Biosynthesis ; Biosynthetic Pathways - genetics ; Butirosin Sulfate - biosynthesis ; Carbohydrate Dehydrogenases - chemistry ; Carbohydrate Dehydrogenases - metabolism ; Chemistry ; Crystallization ; Dehydrogenases ; DNA Primers - genetics ; Enzymes ; Hydrogen ; Hydrogen bonds ; Iron Compounds - metabolism ; Models, Molecular ; Molecular Structure ; molybdenum ; Oxidation ; Physical Sciences ; Protein Binding ; Protein Conformation ; Proteins ; S-Adenosylmethionine - metabolism ; Spasms ; Substrates ; Sulfur Compounds - metabolism ; X-radiation</subject><ispartof>Proc. 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USA, 2013-10, Vol.110 (40), p.15949-15954</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 1, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c618t-d88ba2237c0d524d7c2a56287f8eed6098c6054e32f838a8132b8995647c5fde3</citedby><cites>FETCH-LOGICAL-c618t-d88ba2237c0d524d7c2a56287f8eed6098c6054e32f838a8132b8995647c5fde3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/40.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23749694$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23749694$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24048029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1095380$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Goldman, Peter J.</creatorcontrib><creatorcontrib>Grove, Tyler L.</creatorcontrib><creatorcontrib>Booker, Squire J.</creatorcontrib><creatorcontrib>Drennan, Catherine L.</creatorcontrib><creatorcontrib>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><title>X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry</title><title>Proc. Natl. Acad. Sci. USA</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The 2-deoxy- scyllo -inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine–containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S -adenosyl- l -methionine (AdoMet) radical enzyme. To examine how BtrN employs AdoMet radical chemistry, we have determined its structure with AdoMet and substrate to 1.56 Å resolution. We find a previously undescribed modification to the core AdoMet radical fold: instead of the canonical (β/α) ₆ architecture, BtrN displays a (β ₅/α ₄) motif. We further find that an auxiliary [4Fe-4S] cluster in BtrN, thought to bind substrate, is instead implicated in substrate–radical oxidation. High structural homology in the auxiliary cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofactor biosynthetic enzyme MoaA provides support for the establishment of an AdoMet radical structural motif that is likely common to ∼6,400 uncharacterized AdoMet radical enzymes.</description><subject>aminoglycoside antibiotics</subject><subject>Aminoglycosides</subject><subject>Bacillus - enzymology</subject><subject>Bacillus circulans</subject><subject>Bacteria</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Biosynthesis</subject><subject>Biosynthetic Pathways - genetics</subject><subject>Butirosin Sulfate - biosynthesis</subject><subject>Carbohydrate Dehydrogenases - chemistry</subject><subject>Carbohydrate Dehydrogenases - metabolism</subject><subject>Chemistry</subject><subject>Crystallization</subject><subject>Dehydrogenases</subject><subject>DNA Primers - genetics</subject><subject>Enzymes</subject><subject>Hydrogen</subject><subject>Hydrogen bonds</subject><subject>Iron Compounds - metabolism</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>molybdenum</subject><subject>Oxidation</subject><subject>Physical Sciences</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Proteins</subject><subject>S-Adenosylmethionine - metabolism</subject><subject>Spasms</subject><subject>Substrates</subject><subject>Sulfur Compounds - metabolism</subject><subject>X-radiation</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkr1vFDEQxVcIRC6BmgqwoKHZZPyxa7tBChFfUoACItFZPq8359OtfbG9SJu_Hh97XICGysX7zRvPzKuqJxhOMXB6tvU6nWKKCSECY7hXLTBIXLdMwv1qAUB4LRhhR9VxSmsAkI2Ah9URYcAEELmohu911BPSXm-m5BIKPVqO2cWQnEdLF9Lk88pmZ5D1t9Ng0ZscP6NoO9s7bxNKOY4mj1Fv0BCy6xPqQ0TnXfhkM4q6c6YoZmUHV8jpUfWg15tkH-_fk-rq3dtvFx_qyy_vP16cX9amxSLXnRBLTQjlBrqGsI4bopuWCN4La7sWpDAtNMxS0gsqtMCULIWUTcu4afrO0pPq9ey7HZeD7Yz1ufxQbaMbdJxU0E79rXi3Utfhh6JcYk7bYvBiNggpO5WMy9asTPDemqzKihsqoECv9l1iuBltyqpMaexmo70NY1K4MJhgztv_o4xRKoGBKOjLf9B1GGO5zy8KWCM57HqfzZQpp0rR9ofhMKhdNNQuGuouGqXi2Z87OfC_s1AAtAd2lQe74seKZSPZDnk6I-uUQ7yzoJzJVrKiP5_1Xgelr6NL6uorAdwCYEYwpvQnnBnSeQ</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Goldman, Peter J.</creator><creator>Grove, Tyler L.</creator><creator>Booker, Squire J.</creator><creator>Drennan, Catherine L.</creator><general>National Academy of Sciences</general><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>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry</title><author>Goldman, Peter J. ; Grove, Tyler L. ; Booker, Squire J. ; Drennan, Catherine L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c618t-d88ba2237c0d524d7c2a56287f8eed6098c6054e32f838a8132b8995647c5fde3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>aminoglycoside antibiotics</topic><topic>Aminoglycosides</topic><topic>Bacillus - enzymology</topic><topic>Bacillus circulans</topic><topic>Bacteria</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Biosynthesis</topic><topic>Biosynthetic Pathways - genetics</topic><topic>Butirosin Sulfate - biosynthesis</topic><topic>Carbohydrate Dehydrogenases - chemistry</topic><topic>Carbohydrate Dehydrogenases - metabolism</topic><topic>Chemistry</topic><topic>Crystallization</topic><topic>Dehydrogenases</topic><topic>DNA Primers - genetics</topic><topic>Enzymes</topic><topic>Hydrogen</topic><topic>Hydrogen bonds</topic><topic>Iron Compounds - metabolism</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>molybdenum</topic><topic>Oxidation</topic><topic>Physical Sciences</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Proteins</topic><topic>S-Adenosylmethionine - metabolism</topic><topic>Spasms</topic><topic>Substrates</topic><topic>Sulfur Compounds - metabolism</topic><topic>X-radiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goldman, Peter J.</creatorcontrib><creatorcontrib>Grove, Tyler L.</creatorcontrib><creatorcontrib>Booker, Squire J.</creatorcontrib><creatorcontrib>Drennan, Catherine L.</creatorcontrib><creatorcontrib>Argonne National Lab. (ANL), Argonne, IL (United States). 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Natl. Acad. Sci. USA</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goldman, Peter J.</au><au>Grove, Tyler L.</au><au>Booker, Squire J.</au><au>Drennan, Catherine L.</au><aucorp>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry</atitle><jtitle>Proc. Natl. Acad. Sci. USA</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>110</volume><issue>40</issue><spage>15949</spage><epage>15954</epage><pages>15949-15954</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The 2-deoxy- scyllo -inosamine (DOIA) dehydrogenases are key enzymes in the biosynthesis of 2-deoxystreptamine–containing aminoglycoside antibiotics. In contrast to most DOIA dehydrogenases, which are NAD-dependent, the DOIA dehydrogenase from Bacillus circulans (BtrN) is an S -adenosyl- l -methionine (AdoMet) radical enzyme. To examine how BtrN employs AdoMet radical chemistry, we have determined its structure with AdoMet and substrate to 1.56 Å resolution. We find a previously undescribed modification to the core AdoMet radical fold: instead of the canonical (β/α) ₆ architecture, BtrN displays a (β ₅/α ₄) motif. We further find that an auxiliary [4Fe-4S] cluster in BtrN, thought to bind substrate, is instead implicated in substrate–radical oxidation. High structural homology in the auxiliary cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofactor biosynthetic enzyme MoaA provides support for the establishment of an AdoMet radical structural motif that is likely common to ∼6,400 uncharacterized AdoMet radical enzymes.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>24048029</pmid><doi>10.1073/pnas.1312228110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | aminoglycoside antibiotics Aminoglycosides Bacillus - enzymology Bacillus circulans Bacteria Biochemistry Biological Sciences Biosynthesis Biosynthetic Pathways - genetics Butirosin Sulfate - biosynthesis Carbohydrate Dehydrogenases - chemistry Carbohydrate Dehydrogenases - metabolism Chemistry Crystallization Dehydrogenases DNA Primers - genetics Enzymes Hydrogen Hydrogen bonds Iron Compounds - metabolism Models, Molecular Molecular Structure molybdenum Oxidation Physical Sciences Protein Binding Protein Conformation Proteins S-Adenosylmethionine - metabolism Spasms Substrates Sulfur Compounds - metabolism X-radiation |
| title | X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry |
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