Conformational stability and thermodynamic characterization of the lipoic acid bearing domain of human mitochondrial branched chain α-ketoacid dehydrogenase

Mandar T. Naik, Tai-huang Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The lipoic acid bearing domain (hbLBD) of human mitochondrial branched chain α-ketoacid dehydrogenase (BCKD) plays important role of substrate channeling in oxidative decarboxylation of the branched chain α-ketoacids. Recently hbLBD has been found to follow two-step folding mechanism without detectable presence of stable or kinetic intermediates. The present study describes the conformational stability underlying the folding of this small β-barrel domain. Thermal denaturation in presence of urea and isothermal urea denaturation titrations are used to evaluate various thermodynamic parameters defining the equilibrium unfolding. The linear extrapolation model successfully describes the two-step; native state ↔ denatured state unfolding transition of hbLBD. The average temperature of maximum stability of hbLBD is estimated as 295.6 ± ;0.9 K. Cold denaturation of hbLBD is also predicted and discussed.

Original languageEnglish
Pages (from-to)2483-2492
Number of pages10
JournalProtein Science
Volume13
Issue number9
DOIs
Publication statusPublished - 2004 Sep 1

Keywords

  • BCKD
  • Branched chain α-keto-acid dehydrogenase
  • Lipoic acid bearing domain
  • MSUD
  • Maple syrup urine disease
  • Protein conformational stability
  • hbLBD

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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