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

Biophys Chem. 2005 Apr 1;115(2-3):241-5. doi: 10.1016/j.bpc.2004.12.031. Epub 2005 Jan 6.


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.-

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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