1k8m
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Solution Structure of the Lipoic Acid-Bearing Domain of the E2 component of Human, Mitochondrial Branched-Chain alpha-Ketoacid Dehydrogenase
OverviewOverview
The lipoyl-bearing domain (LBD) of the transacylase (E2) subunit of the, branched-chain alpha-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 alpha-keto, acid dehydrogenase complex (hbLBD). Similar to LBD from other members of, the alpha-keto acid dehydrogenase family, the solution structure of hbLBD, is a flattened beta-barrel formed by two four-stranded antiparallel, beta-sheets. The lipoyl Lys(44) residue resides at the tip of a, beta-hairpin comprising a sharp type I beta-turn and the two connecting, beta-strands 4 and 5. A prominent V-shaped groove formed by a surface, loop, L1, connecting beta 1- and beta 2-strands and the lipoyl lysine, beta-hairpin constitutes the functional pocket. We further applied reduced, spectral density functions formalism to extract dynamic information of, hbLBD from (15)N-T(1), (15)N-T(2), and ((1)H-(15)N) nuclear Overhauser, effect data obtained at 600 MHz. The results showed that residues, surrounding the lipoyl lysine region comprising the L1 loop and the, Lys(44) beta-turn are highly flexible, whereas beta-sheet S1 appears to, display a slow conformational exchange process.
DiseaseDisease
Known diseases associated with this structure: Maple syrup urine disease, type II OMIM:[248610]
About this StructureAbout this Structure
1K8M is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex., Chang CF, Chou HT, Chuang JL, Chuang DT, Huang TH, J Biol Chem. 2002 May 3;277(18):15865-73. Epub 2002 Feb 11. PMID:11839747
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