Structure of the Flavin Adduct Formed in the Suicide Reaction of α-Hydroxybutynoate with D-Lactate Dehydrogenase

Lade...
Vorschaubild
Datum
1979
Autor:innen
Ghisla, Sandro
Olson, Steven T.
Massey, Vincent
Lhoste, Jean-Marc
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
DOI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Green
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Biochemistry. 1979, 18(21), pp. 4733-4742. ISSN 0006-2960. eISSN 1520-4995. Available under: doi: 10.1021/bi00588a038
Zusammenfassung

The Zn-dependent flavoenzyme D-lactate dehydrogenase from Megasphaera elsdenii is irreversibly inactivated by the D form of the suicide substrate 2-hydroxy- 3-butynoic acid. The process of inactivation involves formation of a new pink chromophore, which can be released in intact form from the protein and which was purified to homogeneity by affinity chromatography. Inactivation involves covalent addition of the suicide substrate to the flavin coenzyme. The optical spectra indicate an elongation of the flavin chromophore, and the chemical reactivity suggests a derivative of reduced flavin. The structure of this adduct was deduced from Fourier transform NMR, from the chemical properties, and from comparison with appropriate models, which were synthesized chemically. This structure involves the covalent linkage of the acetylenic inhibitor to positions N(5) and C(6) of the flavin coenzyme via carbon atoms 2 and 4 of the in- hibitor to form an additional fused aromatic ring. The pink adduct can be reconverted to an isoalloxazine chromophore by reduction with borohydride and subsequent reoxidation with oxygen. This new isoalloxazine has the spectral properties of an isoflavin, and it is proposed to carry the moiety of the inactivator molecule as substituent at position C(6). The structure of the pink chromophore representing a cyclic adduct to the flavin positions N(5) and C(6) is compared to that of the adduct obtained from L-lactate oxidase from Mycobacterium smegmatis and the L form of the same inhibitor [C(4a)-N(5) cyclic adduct; Schonbrunn, A,, Abeles, R. H., Walsh, C. T., Ghisla, S., Ogata, H., and Massey, V. (1976) Biochemistry 15, 1978], This comparison allows deductions about the relative orientation of substrate, coenzyme, and active center functional groups in the two enzymes.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690GHISLA, Sandro, Steven T. OLSON, Vincent MASSEY, Jean-Marc LHOSTE, 1979. Structure of the Flavin Adduct Formed in the Suicide Reaction of α-Hydroxybutynoate with D-Lactate Dehydrogenase. In: Biochemistry. 1979, 18(21), pp. 4733-4742. ISSN 0006-2960. eISSN 1520-4995. Available under: doi: 10.1021/bi00588a038
BibTex
@article{Ghisla1979Struc-8157,
  year={1979},
  doi={10.1021/bi00588a038},
  title={Structure of the Flavin Adduct Formed in the Suicide Reaction of α-Hydroxybutynoate with D-Lactate Dehydrogenase},
  number={21},
  volume={18},
  issn={0006-2960},
  journal={Biochemistry},
  pages={4733--4742},
  author={Ghisla, Sandro and Olson, Steven T. and Massey, Vincent and Lhoste, Jean-Marc}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/8157">
    <dc:contributor>Ghisla, Sandro</dc:contributor>
    <dcterms:bibliographicCitation>First publ. in: Biochemistry 18 (1979), 21, pp. 4733 - 4742</dcterms:bibliographicCitation>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/2.0/"/>
    <dc:creator>Ghisla, Sandro</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:41:02Z</dc:date>
    <dc:format>application/pdf</dc:format>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8157/1/Biochemistry_1979_GhislaStructure_of_the_flavin_adduct.pdf"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Olson, Steven T.</dc:creator>
    <dcterms:issued>1979</dcterms:issued>
    <dcterms:abstract xml:lang="eng">The Zn-dependent flavoenzyme D-lactate dehydrogenase from Megasphaera elsdenii is irreversibly inactivated by the D form of the suicide substrate 2-hydroxy- 3-butynoic acid. The process of inactivation involves formation of a new pink chromophore, which can be released in intact form from the protein and which was purified to homogeneity by affinity chromatography. Inactivation involves covalent addition of the suicide substrate to the flavin coenzyme. The optical spectra indicate an elongation of the flavin chromophore, and the chemical reactivity suggests a derivative of reduced flavin. The structure of this adduct was deduced from Fourier transform NMR, from the chemical properties, and from comparison with appropriate models, which were synthesized chemically. This structure involves the covalent linkage of the acetylenic inhibitor to positions N(5) and C(6) of the flavin coenzyme via carbon atoms 2 and 4 of the in- hibitor to form an additional fused aromatic ring. The pink adduct can be reconverted to an isoalloxazine chromophore by reduction with borohydride and subsequent reoxidation with oxygen. This new isoalloxazine has the spectral properties of an isoflavin, and it is proposed to carry the moiety of the inactivator molecule as substituent at position C(6). The structure of the pink chromophore representing a cyclic adduct to the flavin positions N(5) and C(6) is compared to that of the adduct obtained from L-lactate oxidase from Mycobacterium smegmatis and the L form of the same inhibitor [C(4a)-N(5) cyclic adduct; Schonbrunn, A,, Abeles, R. H., Walsh, C. T., Ghisla, S., Ogata, H., and Massey, V. (1976) Biochemistry 15, 1978], This comparison allows deductions about the relative orientation of substrate, coenzyme, and active center functional groups in the two enzymes.</dcterms:abstract>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:language>eng</dc:language>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:41:02Z</dcterms:available>
    <dcterms:title>Structure of the Flavin Adduct Formed in the Suicide Reaction of α-Hydroxybutynoate with D-Lactate Dehydrogenase</dcterms:title>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8157"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8157/1/Biochemistry_1979_GhislaStructure_of_the_flavin_adduct.pdf"/>
    <dc:contributor>Lhoste, Jean-Marc</dc:contributor>
    <dc:contributor>Olson, Steven T.</dc:contributor>
    <dc:rights>Attribution-NonCommercial-NoDerivs 2.0 Generic</dc:rights>
    <dc:creator>Lhoste, Jean-Marc</dc:creator>
    <dc:creator>Massey, Vincent</dc:creator>
    <dc:contributor>Massey, Vincent</dc:contributor>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Diese Publikation teilen