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Nuclear Magnetic Resonance Approaches in the Study of 2-Oxo Acid Dehydrogenase Multienzyme Complexes—A Literature Review
Department of Chemistry, Rutgers University, Newark, NJ 07102, USA
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA
* Author to whom correspondence should be addressed.
Received: 30 July 2013; in revised form: 14 September 2013 / Accepted: 16 September 2013 / Published: 26 September 2013
Abstract: The 2-oxoacid dehydrogenase complexes (ODHc) consist of multiple copies of three enzyme components: E1, a 2-oxoacid decarboxylase; E2, dihydrolipoyl acyl-transferase; and E3, dihydrolipoyl dehydrogenase, that together catalyze the oxidative decarboxylation of 2-oxoacids, in the presence of thiamin diphosphate (ThDP), coenzyme A (CoA), Mg2+ and NAD+, to generate CO2, NADH and the corresponding acyl-CoA. The structural scaffold of the complex is provided by E2, with E1 and E3 bound around the periphery. The three principal members of the family are pyruvate dehydrogenase (PDHc), 2-oxoglutarate dehydrogenase (OGDHc) and branched-chain 2-oxo acid dehydrogenase (BCKDHc). In this review, we report application of NMR-based approaches to both mechanistic and structural issues concerning these complexes. These studies revealed the nature and reactivity of transient intermediates on the enzymatic pathway and provided site-specific information on the architecture and binding specificity of the domain interfaces using solubilized truncated domain constructs of the multi-domain E2 component in its interactions with the E1 and E3 components. Where studied, NMR has also provided information about mobile loops and the possible relationship of mobility and catalysis.
Keywords: 2-oxoacid dehydrogenase complex; pyruvate dehydrogenase complex; thiamin diphosphate; protein-protein interaction; substrate channeling; lipoyl domain; peripheral subunit binding domain; NMR
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Kumaran, S.; Patel, M.S.; Jordan, F. Nuclear Magnetic Resonance Approaches in the Study of 2-Oxo Acid Dehydrogenase Multienzyme Complexes—A Literature Review. Molecules 2013, 18, 11873-11903.
Kumaran S, Patel MS, Jordan F. Nuclear Magnetic Resonance Approaches in the Study of 2-Oxo Acid Dehydrogenase Multienzyme Complexes—A Literature Review. Molecules. 2013; 18(10):11873-11903.
Kumaran, Sowmini; Patel, Mulchand S.; Jordan, Frank. 2013. "Nuclear Magnetic Resonance Approaches in the Study of 2-Oxo Acid Dehydrogenase Multienzyme Complexes—A Literature Review." Molecules 18, no. 10: 11873-11903.