Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain α-keto acid dehydrogenase complex

Chi Fon Chang, Hui Ting Chou, Jacinta L. Chuang, David T. Chuang, Tai Huang Huang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The lipoyl-bearing domain (LBD) of the transacylase (E2) subunit of the branched-chain α-keto acid dehydrogenase complex plays a central role in substrate channeling in this mitochondrial multienzyme complex. We have employed multidimensional heteronuclear NMR techniques to determine the structure and dynamics of the LBD of the human branched-chain α-keto acid dehydrogenase complex (hbLBD). Similar to LBD from other members of the α-keto acid dehydrogenase family, the solution structure of hbLBD is a flattened β-barrel formed by two four-stranded antiparallel β-sheets. The lipoyl Lys44 residue resides at the tip of a β-hairpin comprising a sharp type I β-turn and the two connecting β-strands 4 and 5. A prominent V-shaped groove formed by a surface loop, L1, connecting β1- and β2-strands and the lipoyl lysine β-hairpin constitutes the functional pocket. We further applied reduced spectral density functions formalism to extract dynamic information of hbLBD from 15N-T1, 15N-T2, and (1H-15N) nuclear Over-hauser effect data obtained at 600 MHz. The results showed that residues surrounding the lipoyl lysine region comprising the L1 loop and the Lys44 β-turn are highly flexible, whereas β-sheet S1 appears to display a slow conformational exchange process.

Original languageEnglish (US)
Pages (from-to)15865-15873
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002

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Bearings (structural)
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Thioctic Acid
Lysine
Multienzyme Complexes
Biomolecular Nuclear Magnetic Resonance
Keto Acids
Oxidoreductases
Spectral density
Probability density function
Nuclear magnetic resonance
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain α-keto acid dehydrogenase complex. / Chang, Chi Fon; Chou, Hui Ting; Chuang, Jacinta L.; Chuang, David T.; Huang, Tai Huang.

In: Journal of Biological Chemistry, Vol. 277, No. 18, 03.05.2002, p. 15865-15873.

Research output: Contribution to journalArticle

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