Isocitrate dehydrogenase structures

JH Hurley, RD Chen, AM Dean. Determinants of cofactor specificity in isocitrate dehydrogenase structure of an engineered NADP —> NAD specificity-reversal mutant. Biochemistry 35 5670-5678, 1996. 

A listing of the enzymes and proteins believed to be Mn activated has been published but undoubtedly other examples exist. Structurally characterized, Mn-activated enzymes and proteins which are not included here include dioxygenases, integrins, muconate cycloisome-rase, and isocitrate dehydrogenase. ... 

An understanding of the molecular basis for regulation of isocitrate dehydrogenase by phosphorylation was facilitated by X-ray crystallography of the phosphorylated enzyme in complex with isocitrate. The crystal structures of mutants of the enzyme in which SerllS had been exchanged for aspartate or glutamate were also solved (Hurley et al., 1990). The structure of the enzyme in complex with the substrate isocitrate revealed the phophorylation site to be localized near isocitrate. SerllS itself binds the substrate directly via a H-bond with the O of isocitrate (fig. 2.13). 

Singh, S.K. Matsuno, K. LaPorte, D.C. Banaszak, L.J. Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase. J. Biol. Chem., 276, 26154-26163 (2001)... 

Structural Similarity Between Binding Sites in Influenza Sialidase and Isocitrate Dehydrogenase... 

RD Chen, P Gadal. Structure, function and regulation ofNAD- and NADP-isocitrate dehydrogenases in higher plants and in other organisms. Plant Physiol Biochem 28 411-427, 1990. 

JH Hurley, P Thorsness, V Ramalingham, N Helmers, DE Koshland Jr, RM Stroud. Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. Proc Natl Acad Sci (USA) 86 8635-8639, 1989. 

RD Chen, A Greer, AD Dean. Structural constraints in protein engineering the coenzyme specificity of Escherichia coli isocitrate dehydrogenase. Eur J Biochem 250 578-582, 1997. 

JH Hurley, AM Dean, DE Koshland Jr, RM Stroud. Catalytic mechanism of NADP+-dependent isocitrate dehydrogenase implications from the structures of magnesium-isocitrate and NADP+ complexes. Biochemistry 30 8671-8678, 1991. 

BL Stoddard, AM Dean, DE Koshland Jr. Structure of isocitrate dehydrogenase with isocitrate, nicotinamide adenine dinucleotide phosphate, and calcium at 2.5-A resolution a pseudo-Michaelis ternary complex. Biochemistry 32 9310-9316, 1993. 

JM Bolduc, DH Dyer, WG Scott, P Singer, RM Sweet, DE Koshland Jr, BL Stoddard. Mutagenesis and Laue structures of enzyme intermediates isocitrate dehydrogenase. Science 268 1312-1318, 1995. 

DA Keys, L McAlister-Henn. Subunit structure, expression, and function of NAD(H)-specific isocitrate dehydrogenase in Saccharomyces cerevisiae. JBacteriol 172 4280-4287, 1990. 

M Lancien, P Gadal, M Hodges. Molecular characterization of higher plant NAD-dependent isocitrate dehydrogenase evidence for a heteromeric structure by the complementation of yeast mutants. Plant J 16 325-333, 1998. 

BL Stoddard, AM Dean, DE Koshland Jr. Structure of isocitrate dehydrogenase with... 

The enzymes of the TCA cycle rely heavily on coenzymes for their catalytic function. Isocitrate dehydrogenase and malate dehydrogenase use NAD as a coenzyme, and succinate dehydrogenase uses FAD. Citrate synthase catalyzes a reaction that uses a CoA derivative, acetyl CoA. The a-ketoglutarate dehydrogenase complex uses thiamine pyrophosphate, lipoate and FAD as bound coenzymes, and NAD and CoASEl as substrates. Each of these coenzymes has unique structural features that enable it to fulfill its role in the TCA cycle. 

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