Structural basis for expanded substrate specificities of human long chain acyl-CoA dehydrogenase and related acyl-CoA dehydrogenases.

Substrate Specificity Humans Acyl-CoA Dehydrogenase, Long-Chain / metabolism Models, Molecular Crystallography, X-Ray Catalytic Domain Acyl-CoA Dehydrogenases / metabolism Protein Conformation Amino Acid Sequence

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
05 06 2024
Historique:
received: 23 02 2024
accepted: 23 05 2024
medline: 6 6 2024
pubmed: 6 6 2024
entrez: 5 6 2024
Statut: epublish

Résumé

Crystal structures of human long-chain acyl-CoA dehydrogenase (LCAD) and the catalytically inactive Glu291Gln mutant, have been determined. These structures suggest that LCAD harbors functions beyond its historically defined role in mitochondrial β-oxidation of long and medium-chain fatty acids. LCAD is a homotetramer containing one FAD per 43 kDa subunit with Glu291 as the catalytic base. The substrate binding cavity of LCAD reveals key differences which makes it specific for longer and branched chain substrates. The presence of Pro132 near the start of the E helix leads to helix unwinding that, together with adjacent smaller residues, permits binding of bulky substrates such as 3α, 7α, l2α-trihydroxy-5β-cholestan-26-oyl-CoA. This structural element is also utilized by ACAD11, a eucaryotic ACAD of unknown function, as well as bacterial ACADs known to metabolize sterol substrates. Sequence comparison suggests that ACAD10, another ACAD of unknown function, may also share this substrate specificity. These results suggest that LCAD, ACAD10, ACAD11 constitute a distinct class of eucaryotic acyl CoA dehydrogenases.

Identifiants

DOI: 10.1038/s41598-024-63027-6 PMID: 38839792
pubmed: 38839792
doi: 10.1038/s41598-024-63027-6
pii: 10.1038/s41598-024-63027-6
doi:

Substances chimiques

Acyl-CoA Dehydrogenase, Long-Chain EC 1.3.8.8
Acyl-CoA Dehydrogenases EC 1.3.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

12976

Subventions

Organisme : NIH HHS
ID : R35-ES028377
Pays : United States
Organisme : NIH HHS
ID : GM29076
Pays : United States

Informations de copyright

© 2024. The Author(s).

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Auteurs

Beena Narayanan (B)

Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.

Chuanwu Xia (C)

Department of Chemistry and Biochemistry, College of Arts and Sciences, University of North Florida, Jacksonville, FL, 32224, USA.

Ryan McAndrew (R)

Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, 94740, USA.

Anna L Shen (AL)

McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Jung-Ja P Kim (JP)

Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. jjkim@mcw.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Spécificité du substrat › Structural basis for expanded substrate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Structural basis for expanded substrate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Flavoprotéines › Long-chain-acyl-CoA dehydrogenase › Structural basis for expanded substrate...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Structural basis for expanded substrate...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › Structural basis for expanded substrate...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › Structural basis for expanded substrate...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxidoreductases acting on CH-CH group donors › Acyl-CoA dehydrogenases › Structural basis for expanded substrate...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structural basis for expanded substrate...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Structural basis for expanded substrate...