Publikation:

Medium-Long-Chain Chimeric Human Acyl-CoA Dehydrogenase: Medium-Chain Enzyme with the Active Center Base Arrangement of Long-Chain Acyl-CoA Dehydrogenase

Lade...
Vorschaubild

Datum

1996

Autor:innen

Nandy, Andreas
Kieweg, Volker
Kräutle, Franz-Georg
Vock, Petra
Küchler, Burkhard
Bross, Peter
Kim, Jung-Ja P.
Rasched, Ihab

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

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Biochemistry. 1996, 35(38), pp. 12401-12411. ISSN 0006-2960. eISSN 1520-4995. Available under: doi: 10.1021/bi960785e

Zusammenfassung

The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate α-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH). In long chain acyl-CoA dehydrogenase (LCADH) and isovaleryl-CoA dehydrogenase (IVDH), the corresponding Glu carrying out the same function is placed at position 255 on the adjacent helix G. These glutamates thus act on substrate approaching from two opposite regions at the active center. We have implemented the topology of LCADH in MCADH by carrying out the two mutations Glu376Gly and Thr255Glu. The resulting chimeric enzyme, "medium-/long" chain acyl-CoA dehydrogenase (MLCADH) has ~20% of the activity of MCADH and ~25% that of LCADH with its best substrates octanoyl-CoA and dodecanoyl-CoA, respectively. MLCADH exhibits an enhanced rate of reoxidation with oxygen, however, with a much narrower substrate chain length specificity that peaks with dodecanoyl-CoA. This is the same maximum as that of LCADH and is thus significantly shifted from that of native MCADH (hexanoyl/octanoyl-CoA). The putative, common ancestor of LCADH and IVDH has two Glu residues, one each at positions 255 and 376. The corresponding MCADH mutant, Thr255Glu (glu/glu-MCADH), is as active as MCADH with octanoyl-CoA; its activity/chain length profile is, however, much narrower. The topology of the Glu as H+ abstracting base seems an important factor in determining chain length specificity and reactivity in acyl-CoA dehydrogenases. The mechanisms underlying these effects are discussed in view of the three-dimensional structure of MLCADH, which is presented in the accompanying paper [Lee et al. (1996) Biochemistry 35, 12412-12420].

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690NANDY, Andreas, Volker KIEWEG, Franz-Georg KRÄUTLE, Petra VOCK, Burkhard KÜCHLER, Peter BROSS, Jung-Ja P. KIM, Ihab RASCHED, Sandro GHISLA, 1996. Medium-Long-Chain Chimeric Human Acyl-CoA Dehydrogenase: Medium-Chain Enzyme with the Active Center Base Arrangement of Long-Chain Acyl-CoA Dehydrogenase. In: Biochemistry. 1996, 35(38), pp. 12401-12411. ISSN 0006-2960. eISSN 1520-4995. Available under: doi: 10.1021/bi960785e
BibTex
@article{Nandy1996Mediu-8464,
  year={1996},
  doi={10.1021/bi960785e},
  title={Medium-Long-Chain Chimeric Human Acyl-CoA Dehydrogenase: Medium-Chain Enzyme with the Active Center Base Arrangement of Long-Chain Acyl-CoA Dehydrogenase},
  number={38},
  volume={35},
  issn={0006-2960},
  journal={Biochemistry},
  pages={12401--12411},
  author={Nandy, Andreas and Kieweg, Volker and Kräutle, Franz-Georg and Vock, Petra and Küchler, Burkhard and Bross, Peter and Kim, Jung-Ja P. and Rasched, Ihab and Ghisla, Sandro}
}
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/123456789/8464">
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Vock, Petra</dc:contributor>
    <dcterms:abstract xml:lang="eng">The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate α-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH). In long chain acyl-CoA dehydrogenase (LCADH) and isovaleryl-CoA dehydrogenase (IVDH), the corresponding Glu carrying out the same function is placed at position 255 on the adjacent helix G. These glutamates thus act on substrate approaching from two opposite regions at the active center. We have implemented the topology of LCADH in MCADH by carrying out the two mutations Glu376Gly and Thr255Glu. The resulting chimeric enzyme, "medium-/long" chain acyl-CoA dehydrogenase (MLCADH) has ~20% of the activity of MCADH and ~25% that of LCADH with its best substrates octanoyl-CoA and dodecanoyl-CoA, respectively. MLCADH exhibits an enhanced rate of reoxidation with oxygen, however, with a much narrower substrate chain length specificity that peaks with dodecanoyl-CoA. This is the same maximum as that of LCADH and is thus significantly shifted from that of native MCADH (hexanoyl/octanoyl-CoA). The putative, common ancestor of LCADH and IVDH has two Glu residues, one each at positions 255 and 376. The corresponding MCADH mutant, Thr255Glu (glu/glu-MCADH), is as active as MCADH with octanoyl-CoA; its activity/chain length profile is, however, much narrower. The topology of the Glu as H+ abstracting base seems an important factor in determining chain length specificity and reactivity in acyl-CoA dehydrogenases. The mechanisms underlying these effects are discussed in view of the three-dimensional structure of MLCADH, which is presented in the accompanying paper [Lee et al. (1996) Biochemistry 35, 12412-12420].</dcterms:abstract>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Kräutle, Franz-Georg</dc:creator>
    <dc:contributor>Küchler, Burkhard</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/2.0/"/>
    <dcterms:bibliographicCitation>First publ. in: Biochemistry 35 (1996), 38, pp. 12401-12411</dcterms:bibliographicCitation>
    <dc:contributor>Ghisla, Sandro</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:issued>1996</dcterms:issued>
    <dc:creator>Rasched, Ihab</dc:creator>
    <dc:creator>Ghisla, Sandro</dc:creator>
    <dc:creator>Bross, Peter</dc:creator>
    <dc:contributor>Rasched, Ihab</dc:contributor>
    <dc:contributor>Nandy, Andreas</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8464/1/Biochemistry_1996_NandyMedium_long_chain_chimeric_human_Acyl_CoA.pdf"/>
    <dc:creator>Kieweg, Volker</dc:creator>
    <dc:contributor>Kim, Jung-Ja P.</dc:contributor>
    <dc:format>application/pdf</dc:format>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8464"/>
    <dcterms:title>Medium-Long-Chain Chimeric Human Acyl-CoA Dehydrogenase: Medium-Chain Enzyme with the Active Center Base Arrangement of Long-Chain Acyl-CoA Dehydrogenase</dcterms:title>
    <dc:creator>Kim, Jung-Ja P.</dc:creator>
    <dc:contributor>Bross, Peter</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:43:52Z</dc:date>
    <dc:creator>Vock, Petra</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:43:52Z</dcterms:available>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8464/1/Biochemistry_1996_NandyMedium_long_chain_chimeric_human_Acyl_CoA.pdf"/>
    <dc:language>eng</dc:language>
    <dc:creator>Küchler, Burkhard</dc:creator>
    <dc:contributor>Kräutle, Franz-Georg</dc:contributor>
    <dc:contributor>Kieweg, Volker</dc:contributor>
    <dc:creator>Nandy, Andreas</dc:creator>
    <dc:rights>Attribution-NonCommercial-NoDerivs 2.0 Generic</dc:rights>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
  </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