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.
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.-
Puisac
Beatriz
B
Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, C/Domingo Miral s/n, E-50009 Zaragoza, Spain.
López-Viñas
Eduardo
E
Moreno
Susana
S
Mir
Cecilia
C
Pérez-Cerdá
Celia
C
Menao
Sebastián
S
Lluch
Dolores
D
Pié
Angeles
A
Gómez-Puertas
Paulino
P
Casals
Nuria
N
Ugarte
Magdalena
M
Hegardt
Faustog
F
Pié
Juan
J
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
D018389:Codon, Nonsense; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase