Title :

On the molecular basis of D-bifunctional protein deficiency type III

Author(s) :

Mehtälä, Maija L. [Auteur]
University of Oulu [Finland] = Oulun yliopisto [Suomi] = Université d'Oulu [Finlande]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Pietikäinen, Laura P. [Auteur]
University of Oulu [Finland] = Oulun yliopisto [Suomi] = Université d'Oulu [Finlande]
Hiltunen, J. Kalervo [Auteur]
University of Oulu [Finland] = Oulun yliopisto [Suomi] = Université d'Oulu [Finlande]
Glumoff, Tuomo [Auteur]
University of Oulu [Finland] = Oulun yliopisto [Suomi] = Université d'Oulu [Finlande]

Journal title :

PLoS One

Abbreviated title :

PLoS ONE

Volume number :

8

Pages :

e53688

Publication date :

2013-01-07

ISSN :

1932-6203

English keyword(s) :

Fatty Acids
Humans
Escherichia coli
Substrate Specificity
Child, Preschool
Male
Structure-Activity Relationship
Recombinant Proteins
Hearing Loss, Sensorineural
Genetic Complementation Test
17-Hydroxysteroid Dehydrogenases
Cloning, Molecular
Female
Child
Catalytic Domain
Oxidation-Reduction
Enzyme Stability
Models, Molecular
Lipid Metabolism
Hydro-Lyases
Peroxisomal Multifunctional Protein-2
Peroxisomes
Gonadal Dysgenesis, 46,XX
Mutation
Kinetics
Saccharomyces cerevisiae

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Molecular basis of D-bifunctional protein (D-BP) deficiency was studied with wild type and five disease-causing variants of 3R-hydroxyacyl-CoA dehydrogenase fragment of the human MFE-2 (multifunctional enzyme type 2) ...
Show more >Molecular basis of D-bifunctional protein (D-BP) deficiency was studied with wild type and five disease-causing variants of 3R-hydroxyacyl-CoA dehydrogenase fragment of the human MFE-2 (multifunctional enzyme type 2) protein. Complementation analysis in vivo in yeast and in vitro enzyme kinetic and stability determinants as well as in silico stability and structural fluctuation calculations were correlated with clinical data of known patients. Despite variations not affecting the catalytic residues, enzyme kinetic performance (K(m), V(max) and k(cat)) of the recombinant protein variants were compromised to a varying extent and this can be judged as the direct molecular cause for D-BP deficiency. Protein stability plays an additional role in producing non-functionality of MFE-2 in case structural variations affect cofactor or substrate binding sites. Structure-function considerations of the variant proteins matched well with the available data of the patients.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Computational Molecular Systems Biology

Submission date :

2020-02-12T15:11:14Z
2021-03-17T09:05:50Z