Nuclear magnetic resonance approaches in the study of 2-oxo acid dehydrogenase multienzyme complexes--a literature review.
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.
Department of Chemistry, Rutgers University, Newark, NJ 07102, USA. frjordan@rutgers.edu.
Sowmini
S
Kumaran
Mulchand S
MS
Patel
Frank
F
Jordan
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000737:chemistry*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D020134:Catalytic Domain; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry*
D001426:Bacterial Proteins; D011768:Pyruvate Dehydrogenase Complex; D007655:Ketoglutarate Dehydrogenase Complex; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)