Digitala Vetenskapliga Arkivet

Driftstörningar
Det förekommer återkommande driftstörningar på några av sök-portalerna på grund av hög belastning. Vi arbetar på att lösa problemet, ni kan tillfälligt mötas av ett felmeddelande.
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Structural enzymological studies of multifunctional enzyme, type-1 (MFE1) with the 2E-decenoyl-CoA and 2E,4E-decadienoyl-CoA substrates: The regeneration of the dehydrogenase catalytic site is the rate limiting step of its combined reactions
Univ Oulu, Fac Biochem & Mol Med, POB 5400, FI-90014 Oulu, Finland..
Univ Wurzburg, Inst Biochem & Mol Biol, Wurzburg, Germany..
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi inom livsvetenskaperna (Kemi LV), Biokemi.ORCID-id: 0000-0002-3203-3793
Univ Oulu, Fac Biochem & Mol Med, POB 5400, FI-90014 Oulu, Finland..
Visa övriga samt affilieringar
2026 (Engelska)Ingår i: Journal of Structural Biology, ISSN 1047-8477, E-ISSN 1095-8657, Vol. 218, nr 3, artikel-id 108346Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The rat peroxisomal multifunctional enzyme, type-1 (RnMFE1) is a monomeric enzyme with two active sites, which catalyze the second and third reaction of the beta-oxidation cycle, being the 2E-enoyl-CoA hydratase (ECH) and the 3S-hydroxyacyl-CoA dehydrogenase (HAD) reaction, respectively. Previous enzyme kinetic studies of MFE1 have shown that MFE1 also degrades 2E,4E-decadienoyl-CoA using a substrate channeling mechanism for transferring the hydrated intermediate between the two active sites. In the current studies, the Michaelis-Menten parameters for the substrate 2E-decenoyl-CoA for the hydratase and dehydrogenase reactions are reported and compared with the corresponding values for 2E,4E-decadienoyl-CoA and 2E-butenoyl-CoA. Also, pre-steady state kinetic data for the dehydrogenase activity for 2E-decenoyl-CoA and 2E,4E-decadienoyl-CoA have been obtained. The kinetic data suggest that the rate determining step of the combined hydratase and dehydrogenase reactions, characterized by the respective kcat-values of the overall reaction of the studied substrates, concerns the regeneration of the HAD active site, after the dehydrogenation step. It is discussed that this kinetic behavior could be related to the dynamical properties of the enzyme. The crystallographic binding studies of RnMFE1 with 2E,4E-decadienoyl-CoA have captured its mode of binding in the ECH active site as a competent enzyme product complex but also as an incompetent enzyme substrate complex. Structural analysis shows that positively charged patches on the enzyme surface between the ECH and HAD active sites would facilitate the channeling of the hydrated intermediate of 2E,4E-decadienoyl-CoA between these sites by electrostatic steering, without being released into the bulk solvent.

Ort, förlag, år, upplaga, sidor
Elsevier, 2026. Vol. 218, nr 3, artikel-id 108346
Nyckelord [en]
beta-Oxidation, Enoyl-CoA hydratase, Enzyme dynamics, Peroxisome, Substrate channeling, Trans fatty acids
Nationell ämneskategori
Molekylärbiologi Strukturbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-594944DOI: 10.1016/j.jsb.2026.108346ISI: 001825539500001PubMedID: 42435994Scopus ID: 2-s2.0-105044467935OAI: oai:DiVA.org:uu-594944DiVA, id: diva2:2094781
Tillgänglig från: 2026-08-24 Skapad: 2026-08-24 Senast uppdaterad: 2026-08-24Bibliografiskt granskad

Open Access i DiVA

fulltext(5299 kB)26 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 5299 kBChecksumma SHA-512
a97d980cac8496c00bfc807f361e63c324615872eea41e22038d369993fbde5534b6e67fdc853d8fdac0cbc1460b9a48fb910d837aaf018d3096e465dbf4ac51
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Sök vidare i DiVA

Av författaren/redaktören
Widersten, Mikael
Av organisationen
Biokemi
I samma tidskrift
Journal of Structural Biology
MolekylärbiologiStrukturbiologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 183 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf