title: Skipping of exon 2 and exons 2 plus 3 of HMG-CoA lyase (HL) gene produces the loss of beta sheets 1 and 2 in the recently proposed (beta-alpha)8 TIM barrel model of HL.
abstract: HMG-CoA lyase (HL) deficiency is a rare autosomal recessive genetic disorder that affects ketogenesis and leucine catabolism. We report a new Spanish patient who bears the frequent nonsense mutation G109T (Mediterranean mutation). This mutation can produce aberrant splicing with three mRNA variants: one of the expected size, the second with deletion of exon 2, and the third with deletion of exons 2 and 3. Recently our group proposed a 3D model for human HL containing a (beta-alpha)(8) (TIM) barrel structure. We have studied the effect of the deletions of exon 2 and exons 2 plus 3 on the proposed HL model. Exon 2 skipping led to the loss of beta-sheet 1, and the skipping of exons 2 and 3 caused the disappearance of alpha helix 1 and beta-sheets 1 and 2.-
authors.affiliation: Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, C/Domingo Miral s/n, E-50009 Zaragoza, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Puisac
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Viñas
authors.forename: Susana
authors.initials: S
authors.lastname: Moreno
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mir
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
authors.forename: Sebastián
authors.initials: S
authors.lastname: Menao
authors.forename: Dolores
authors.initials: D
authors.lastname: Lluch
authors.forename: Angeles
authors.initials: A
authors.lastname: Pié
authors.forename: Paulino
authors.initials: P
authors.lastname: Gómez-Puertas
authors.forename: Nuria
authors.initials: N
authors.lastname: Casals
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
authors.forename: Faustog
authors.initials: F
authors.lastname: Hegardt
authors.forename: Juan
authors.initials: J
authors.lastname: Pié
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D018389:Codon, Nonsense / Q000235:genetics; D005091:Exons / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008958:Models, Molecular; D007652:Oxo-Acid-Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013030:Spain
chemical_list: D018389:Codon, Nonsense; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase