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United States Department of Agriculture

Agricultural Research Service

Title: What a Difference a Methylene-Group Can Make

Authors
item Miernyk, Jan
item Mooney, B - UNIV OF MISSOURI
item Tovar-Mendez, A - UNIV OF MISSOURI
item David, N - UNIV OF MISSOURI
item Randall, D - UNIV OF MISSOURI

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: July 10, 2002
Publication Date: N/A

Technical Abstract: Mitochondria contain three distinct alpha-ketoacid dehydrogenase complexes. The complexes are defined by their substrate specificity: alpha-ketoglutarate, alpha-ketopropionate (pyruvate), and the branched chain alpha-ketoacids derived from Leu, Ile, and Val. We have focused our attention on the pyruvate dehydrogenase complex (PDC) and the branched-chain "-ketoacid dehydrogenase complex (BCKDC). Both complexes comprise multiple copies of three component enzymes: "-ketoacid dehydrogenase/decarboxylase (E1), dihydrolipoyl acyltransferase (E2), and dihydrolipoyl dehydrogenase (E3). The E2 subunits associate to form the very large geometric core structures of the complexes. The E1 (an a2b2 heterotetramer) and E3 (a homodimer) enzymes associate non-covalently with the E2 core structure at specific binding sites and with fixed stoichiometries. Substrate-channeling plus active-site coupling result in very high catalytic efficiencies. Assembly of the complex core structures is a sequential process. The E2 monomers associate forming trimers, via specific regions within the catalytic domain. The trimers then further associate, forming either a pentagonal dodecahedron (PDC) or a cube (BCKDC). The primary sequences of Arabidopsis thaliana PDC E2 and BCKDC E2 are 25% identical and 43% similar, and both associate into trimers. However, the sequence information that subsequently defines which final structure will be formed has not yet been defined. The elaborate catalytic architecture of the mitochondrial alpha-ketoacid dehydrogenase complexes has been retained for multiple metabolic functions. At the same time, there has been specialization/differentiation of protein structures and regulatory mechanisms.

Last Modified: 10/22/2014
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