Structure of the branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction
Identifieur interne : 000439 ( Main/Corpus ); précédent : 000438; suivant : 000440Structure of the branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction
Auteurs : Catrine L. Berthold ; Dörte Gocke ; Martin D. Wood ; Finian J. Leeper ; Martina Pohl ; Gunter SchneiderSource :
- Acta Crystallographica Section D [ 1399-0047 ] ; 2007-12.
English descriptors
Abstract
The thiamin diphosphate (ThDP) dependent branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis catalyzes the decarboxylation of 3‐methyl‐2‐oxobutanoic acid to 3‐methylpropanal (isobutyraldehyde) and CO2. The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. The crystal structures provide insights into the structural basis of substrate selectivity and stereoselectivity of the enzyme and thus are suitable as a framework for the redesign of the substrate profile in carboligation reactions.
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DOI: 10.1107/S0907444907050433
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ISTEX:B6FD04F98A98592A24220E74396230C87C04639FLe document en format XML
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Leeper</name></author><author><name sortKey="Pohl, Martina" sort="Pohl, Martina" uniqKey="Pohl M" first="Martina" last="Pohl">Martina Pohl</name></author><author><name sortKey="Schneider, Gunter" sort="Schneider, Gunter" uniqKey="Schneider G" first="Gunter" last="Schneider">Gunter Schneider</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B6FD04F98A98592A24220E74396230C87C04639F</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1107/S0907444907050433</idno><idno type="url">https://api.istex.fr/document/B6FD04F98A98592A24220E74396230C87C04639F/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000439</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Structure of the branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction</title><author><name sortKey="Berthold, Catrine L" sort="Berthold, Catrine L" uniqKey="Berthold C" first="Catrine L." last="Berthold">Catrine L. 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D</title><idno type="ISSN">1399-0047</idno><idno type="eISSN">1399-0047</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>5 Abbey Square, Chester, Cheshire CH1 2HU, England</pubPlace><date type="published" when="2007-12">2007-12</date><biblScope unit="volume">63</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1217">1217</biblScope><biblScope unit="page" to="1224">1224</biblScope></imprint><idno type="ISSN">1399-0047</idno></series><idno type="istex">B6FD04F98A98592A24220E74396230C87C04639F</idno><idno type="DOI">10.1107/S0907444907050433</idno><idno type="ArticleID">AYDHV5093</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1399-0047</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>biocatalysis.</term><term>carboligation</term><term>stereoselectivity</term><term>thiamin diphosphate</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The thiamin diphosphate (ThDP) dependent branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis catalyzes the decarboxylation of 3‐methyl‐2‐oxobutanoic acid to 3‐methylpropanal (isobutyraldehyde) and CO2. The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. The crystal structures provide insights into the structural basis of substrate selectivity and stereoselectivity of the enzyme and thus are suitable as a framework for the redesign of the substrate profile in carboligation reactions.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Catrine L. Berthold</name><affiliations><json:string>Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S‐17177 Stockholm, Sweden</json:string><json:string>Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Research Center Jülich, 52426 Jülich, Germany</json:string><json:string>Cambridge University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, England</json:string></affiliations></json:item><json:item><name>Dörte Gocke</name><affiliations><json:string>Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S‐17177 Stockholm, Sweden</json:string><json:string>Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Research Center Jülich, 52426 Jülich, Germany</json:string><json:string>Cambridge University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, England</json:string></affiliations></json:item><json:item><name>Martin D. Wood</name><affiliations><json:string>Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S‐17177 Stockholm, Sweden</json:string><json:string>Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Research Center Jülich, 52426 Jülich, Germany</json:string><json:string>Cambridge University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, England</json:string></affiliations></json:item><json:item><name>Finian J. 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The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. 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D</title><idno type="pISSN">1399-0047</idno><idno type="eISSN">1399-0047</idno><idno type="DOI">10.1111/(ISSN)1399-0047</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>5 Abbey Square, Chester, Cheshire CH1 2HU, England</pubPlace><date type="published" when="2007-12"></date><biblScope unit="volume">63</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1217">1217</biblScope><biblScope unit="page" to="1224">1224</biblScope></imprint></monogr><idno type="istex">B6FD04F98A98592A24220E74396230C87C04639F</idno><idno type="DOI">10.1107/S0907444907050433</idno><idno type="ArticleID">AYDHV5093</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The thiamin diphosphate (ThDP) dependent branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis catalyzes the decarboxylation of 3‐methyl‐2‐oxobutanoic acid to 3‐methylpropanal (isobutyraldehyde) and CO2. The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. 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D</title></titleGroup></publicationMeta><publicationMeta level="part" position="12012"><doi origin="wiley">10.1111/ayd.2007.63.issue-12</doi><numberingGroup><numbering type="journalVolume" number="63">63</numbering><numbering type="journalIssue" number="12">12</numbering></numberingGroup><coverDate startDate="2007-12">December 2007</coverDate></publicationMeta><publicationMeta level="unit" type="miscellaneous" position="3" status="forIssue"><doi origin="wiley">10.1107/S0907444907050433</doi><idGroup><id type="unit" value="AYDHV5093"></id><id type="society" value="hv5093"></id></idGroup><titleGroup><title type="tocHeading1">research papers</title></titleGroup><eventGroup><event type="firstOnline" date="2007-12-07"></event><event type="publishedOnlineFinalForm" date="2007-12-07"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:Header result:Header" date="2010-02-28"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-06"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="1217">1217</numbering><numbering type="pageLast" number="1224">1224</numbering></numberingGroup><correspondenceTo>Gunter Schneider, e‐mail: <email>gunter.schneider@ki.se</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:AYD2.AYDhv5093.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 31 August 2007, accepted 15 October 2007</unparsedEditorialHistory><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="wordTotal" number="0"></count><count type="referenceTotal" number="0"></count><count type="linksCrossRef" number="0"></count><count type="linksPubMed" number="0"></count></countGroup><titleGroup><title type="main">Structure of the branched‐chain keto acid decarboxylase (KdcA) from <i>Lactococcus lactis</i> provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction</title><title type="shortAuthors">Berthold <i>et al.</i></title><title type="short">KdcA</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1"><personName><givenNames>Catrine L.</givenNames><familyName>Berthold</familyName></personName></creator><creator creatorRole="author" xml:id="cr2"><personName><givenNames>Dörte</givenNames><familyName>Gocke</familyName></personName></creator><creator creatorRole="author" xml:id="cr3"><personName><givenNames>Martin D.</givenNames><familyName>Wood</familyName></personName></creator><creator creatorRole="author" xml:id="cr4"><personName><givenNames>Finian J.</givenNames><familyName>Leeper</familyName></personName></creator><creator creatorRole="author" xml:id="cr5"><personName><givenNames>Martina</givenNames><familyName>Pohl</familyName></personName></creator><creator creatorRole="author" xml:id="cr6"><personName><givenNames>Gunter</givenNames><familyName>Schneider</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="SE"><unparsedAffiliation>Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S‐17177 Stockholm, Sweden</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="DE"><unparsedAffiliation>Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Research Center Jülich, 52426 Jülich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="a3"><unparsedAffiliation>Cambridge University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, England</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">thiamin diphosphate</keyword><keyword xml:id="k2">carboligation</keyword><keyword xml:id="k3">stereoselectivity</keyword><keyword xml:id="k4">biocatalysis.</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p>The thiamin diphosphate (ThDP) dependent branched‐chain keto acid decarboxylase (KdcA) from <i>Lactococcus lactis</i> catalyzes the decarboxylation of 3‐methyl‐2‐oxobutanoic acid to 3‐methylpropanal (isobutyraldehyde) and CO<sub>2</sub>. The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. The crystal structures provide insights into the structural basis of substrate selectivity and stereoselectivity of the enzyme and thus are suitable as a framework for the redesign of the substrate profile in carboligation reactions.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Structure of the branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction</title></titleInfo><titleInfo type="abbreviated"><title>KdcA</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Structure of the branched‐chain keto acid decarboxylase (KdcA) from</title></titleInfo><name type="personal"><namePart type="given">Catrine L.</namePart><namePart type="family">Berthold</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dörte</namePart><namePart type="family">Gocke</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin D.</namePart><namePart type="family">Wood</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Finian J.</namePart><namePart type="family">Leeper</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martina</namePart><namePart type="family">Pohl</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gunter</namePart><namePart type="family">Schneider</namePart><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="miscellaneous"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">5 Abbey Square, Chester, Cheshire CH1 2HU, England</placeTerm></place><dateIssued encoding="w3cdtf">2007-12</dateIssued><edition>Received 31 August 2007, accepted 15 October 2007</edition><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">The thiamin diphosphate (ThDP) dependent branched‐chain keto acid decarboxylase (KdcA) from Lactococcus lactis catalyzes the decarboxylation of 3‐methyl‐2‐oxobutanoic acid to 3‐methylpropanal (isobutyraldehyde) and CO2. The enzyme is also able to catalyze carboligation reactions with an exceptionally broad substrate range, a feature that makes KdcA a potentially valuable biocatalyst for C—C bond formation, in particular for the enzymatic synthesis of diversely substituted 2‐hydroxyketones with high enantioselectivity. The crystal structures of recombinant holo‐KdcA and of a complex with an inhibitory ThDP analogue mimicking a reaction intermediate have been determined to resolutions of 1.6 and 1.8 Å, respectively. KdcA shows the fold and cofactor–protein interactions typical of thiamin‐dependent enzymes. In contrast to the tetrameric assembly displayed by most other ThDP‐dependent decarboxylases of known structure, KdcA is a homodimer. The crystal structures provide insights into the structural basis of substrate selectivity and stereoselectivity of the enzyme and thus are suitable as a framework for the redesign of the substrate profile in carboligation reactions.</abstract><subject lang="en"><genre>Keywords</genre><topic>thiamin diphosphate</topic><topic>carboligation</topic><topic>stereoselectivity</topic><topic>biocatalysis.</topic></subject><relatedItem type="host"><titleInfo><title>Acta Crystallographica Section D</title></titleInfo><titleInfo type="abbreviated"><title>Acta Cryst. D</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">1399-0047</identifier><identifier type="eISSN">1399-0047</identifier><identifier type="DOI">10.1111/(ISSN)1399-0047</identifier><identifier type="PublisherID">AYD2</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>63</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1217</start><end>1224</end></extent></part></relatedItem><identifier type="istex">B6FD04F98A98592A24220E74396230C87C04639F</identifier><identifier type="DOI">10.1107/S0907444907050433</identifier><identifier type="ArticleID">AYDHV5093</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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