Evolutionary Morphing of Tryptophan Synthase : Functional Mechanisms for the Enzymatic Channeling of Indole

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2018
Autor:innen
Schupfner, Michael
Busch, Florian
Baslé, Arnaud
Ehrmann, Alexander
Sterner, Reinhard
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

Tryptophan synthase (TrpS) is a heterotetrameric αββα enzyme that exhibits complex substrate channeling and allosteric mechanisms and is a model system in enzymology. In this work, we characterize proposed early and late evolutionary states of TrpS and show that they have distinct quaternary structures, caused by insertions-deletions of sequence segments (indels) in the β-subunit. Remarkably, indole hydrophobic channels that connect α and β active sites have re-emerged in both TrpS types, yet they follow different paths through the β-subunit fold. Also, both TrpS geometries activate the α-subunit through the rearrangement of loops flanking the active site. Our results link evolutionary sequence changes in the enzyme subunits with channeling and allostery in the TrpS enzymes. The findings demonstrate that indels allow protein quaternary architectures to scape "minima" in the evolutionary landscape, thereby overcoming the conservational constraints imposed by existing functional interfaces and being free to morph into new mechanistic enzymes.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690FLEMING, Jennifer R., Michael SCHUPFNER, Florian BUSCH, Arnaud BASLÉ, Alexander EHRMANN, Reinhard STERNER, Olga MAYANS, 2018. Evolutionary Morphing of Tryptophan Synthase : Functional Mechanisms for the Enzymatic Channeling of Indole. In: Journal of Molecular Biology : JMB. 2018, 430(24), pp. 5066-5079. ISSN 0022-2836. eISSN 1089-8638. Available under: doi: 10.1016/j.jmb.2018.10.013
BibTex
@article{Fleming2018-12Evolu-43692,
  year={2018},
  doi={10.1016/j.jmb.2018.10.013},
  title={Evolutionary Morphing of Tryptophan Synthase : Functional Mechanisms for the Enzymatic Channeling of Indole},
  number={24},
  volume={430},
  issn={0022-2836},
  journal={Journal of Molecular Biology : JMB},
  pages={5066--5079},
  author={Fleming, Jennifer R. and Schupfner, Michael and Busch, Florian and Baslé, Arnaud and Ehrmann, Alexander and Sterner, Reinhard and Mayans, Olga}
}
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/123456789/43692">
    <dc:creator>Baslé, Arnaud</dc:creator>
    <dcterms:title>Evolutionary Morphing of Tryptophan Synthase : Functional Mechanisms for the Enzymatic Channeling of Indole</dcterms:title>
    <dc:contributor>Schupfner, Michael</dc:contributor>
    <dc:creator>Ehrmann, Alexander</dc:creator>
    <dc:contributor>Sterner, Reinhard</dc:contributor>
    <dcterms:issued>2018-12</dcterms:issued>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Sterner, Reinhard</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-11-07T07:43:56Z</dc:date>
    <dc:contributor>Baslé, Arnaud</dc:contributor>
    <dc:creator>Fleming, Jennifer R.</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Schupfner, Michael</dc:creator>
    <dc:contributor>Mayans, Olga</dc:contributor>
    <dc:contributor>Fleming, Jennifer R.</dc:contributor>
    <dc:creator>Mayans, Olga</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-11-07T07:43:56Z</dcterms:available>
    <dcterms:abstract xml:lang="eng">Tryptophan synthase (TrpS) is a heterotetrameric αββα enzyme that exhibits complex substrate channeling and allosteric mechanisms and is a model system in enzymology. In this work, we characterize proposed early and late evolutionary states of TrpS and show that they have distinct quaternary structures, caused by insertions-deletions of sequence segments (indels) in the β-subunit. Remarkably, indole hydrophobic channels that connect α and β active sites have re-emerged in both TrpS types, yet they follow different paths through the β-subunit fold. Also, both TrpS geometries activate the α-subunit through the rearrangement of loops flanking the active site. Our results link evolutionary sequence changes in the enzyme subunits with channeling and allostery in the TrpS enzymes. The findings demonstrate that indels allow protein quaternary architectures to scape "minima" in the evolutionary landscape, thereby overcoming the conservational constraints imposed by existing functional interfaces and being free to morph into new mechanistic enzymes.</dcterms:abstract>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/43692"/>
    <dc:creator>Busch, Florian</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:language>eng</dc:language>
    <dc:contributor>Busch, Florian</dc:contributor>
    <dc:contributor>Ehrmann, Alexander</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
Ja
Begutachtet
Ja
Diese Publikation teilen