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: Beatriz Puisac, Eduardo López-Viñas, Susana Moreno, Cecilia Mir, Celia Pérez-Cerdá, Sebastián Menao, Dolores Lluch, Angeles Pié, Paulino Gómez-Puertas, Nuria Casals, Magdalena Ugarte, Faustog Hegardt, Juan Pié
• Journal: Biophysical chemistry (Biophys Chem) Vol. 115 Issue 2-3 Pg. 241-5 (Apr 01 2005) ISSN: 0301-4622 [Print] Netherlands
• PMID: 15752612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• Oxo-Acid-Lyases
• 3-hydroxy-3-methylglutaryl-coenzyme A lyase

Topics

• Base Sequence
• Binding Sites
• Codon, Nonsense (genetics)
• Exons (genetics)
• Humans
• Infant
• Male
• Models, Molecular
• Oxo-Acid-Lyases (chemistry, genetics, metabolism)
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Spain