On the Enzymatic Activation of NADH

Meijers, Rob; Morris, Richard J.; Adolph, Hans-Werner; Merli, Angelo; Lamzin, Victor S.; Cedergren-Zeppezauer, Eila

doi:10.1074/jbc.m010870200

Cited by 105 publications

(130 citation statements)

References 31 publications

(20 reference statements)

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“…Alcohol dehydrogenases with the Rossmann fold require a metal ion such as Zn 2ϩ bound to the active site to stabilize a transition state such as an alkoxide (43,44). The catalytic reaction of PsDpkA is not accelerated but inhibited by metal ions (24), and no metal ion bound to the protein was detected on the residual electron density map.…”

Section: Resultsmentioning

confidence: 99%

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Goto

Muramatsu

Mihara

et al. 2005

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Goto

Muramatsu

Mihara

et al. 2005

Journal of Biological Chemistry

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“…Although NAD ϩ and NADH differ by only a single proton and two electrons, the structures of the nicotinamide moieties are vastly different. In NAD ϩ , the nicotinamide has a planar structure, whereas it is puckered in NADH (25). This marked difference probably explains the differential binding of the two nucleotides and suggests that the nicotinamide moiety plays an important role in mediating NADH binding.…”

Section: Discussionmentioning

confidence: 99%

Differential binding of NAD ⁺ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor

Fjeld

Birdsong

Goodman

2003

Proc. Natl. Acad. Sci. U.S.A.

262

221

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Carboxyl-terminal binding protein (CtBP) is a transcriptional corepressor originally identified through its ability to interact with adenovirus E1A. The finding that CtBP-E1A interactions were regulated by the nicotinamide adeninine dinucleotides NAD ؉ and NADH raised the possibility that CtBP could serve as a nuclear redox sensor. This model requires differential binding affinities of NAD ؉ and NADH, which has been controversial. The structure of CtBP determined by x-ray diffraction revealed a tryptophan residue adjacent to the proposed nicotinamide adenine dinucleotide binding site. We find that this tryptophan residue shows strong fluorescence resonance energy transfer to bound NADH. In this report, we take advantage of these findings to measure the dissociation constants for CtBP with NADH and NAD ؉ . The affinity of NADH was determined by using fluorescence resonance energy transfer. The binding of NADH to protein is associated with an enhanced intensity of NADH fluorescence and a blue shift in its maximum. NAD ؉ affinity was estimated by measuring the loss of the fluorescence blue shift as NADH dissociates on addition of NAD ؉ . Our studies show a >100-fold higher affinity of NADH than NAD ؉ , consistent with the proposed function of CtBP as a nuclear redox sensor. Moreover, the concentrations of NADH and NAD ؉ required for half-maximal binding are approximately the same as their concentrations in the nuclear compartment. These findings support the possibility that changes in nuclear nicotinamide adenine dinucleotides could regulate the functions of CtBP in cell differentiation, development, or transformation.A n emerging theme in gene regulation is the dependence of transcriptional coregulators on molecules linked to cellular respiration. Acetyl-CoA is required by the histone acetyltransferase coactivators (1) and is perhaps the most central of all intermediary metabolites, bridging the major catabolic and anabolic processes to the Kreb's cycle, where its two carbons are converted to the respiratory product, CO 2 . ATP is important for essentially all cellular processes requiring energy, including the chromatin remodeling proteins involved in modifying nucleosomal structure (2). The pervasive involvement of acetyl-CoA and ATP in cellular processes generally obscures recognition of their specific contributions to transcriptional regulation, however. In addition, the relatively small changes in acetyl-CoA and ATP that occur during metabolism may not be suitable for regulating the activities of the relevant enzymes.The breakdown of carbon sources is also associated with the reduction of the nicotinamide adenine dinucleotide NAD ϩ to NADH. NADH serves as an electron carrier that transports reducing equivalents to the electron transport chain, where ATP is synthesized. The synthesis of ATP involves oxidative phosphorylation, wherein NADH is oxidized to NAD ϩ and molecular oxygen is reduced to water. These roles of NAD ϩ and NADH provide additional, albeit somewhat indirect, connections between energy homeostas...

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“…The nicotinamide ring of NADH/NAD + or NADPH/NADP + is the part of the cofactor directly involved in the transfer of electrons during the reactions catalyzed by NAD(P)H-dependent oxidoreductases, while the C4 carbon atom of the nicotinamide ring acts as the acceptor/ donor of a proton [2]. The addition of the phosphate to the 2′-OH group of the adenine ribose ring in NADPH/NADP + does not modify the electron transport capability as it is located far from the electron transfer region (Fig.…”

Section: Introductionmentioning

confidence: 99%

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Vidal

Kelly

Mordaka

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

233

147

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A B S T R A C T NAD(P)H-dependent oxidoreductases catalyze the reduction or oxidation of a substrate coupled to the oxidation or reduction, respectively, of a nicotinamide adenine dinucleotide cofactor NAD(P)H or NAD(P) + . NAD(P)Hdependent oxidoreductases catalyze a large variety of reactions and play a pivotal role in many central metabolic pathways. Due to the high activity, regiospecificity and stereospecificity with which they catalyze redox reactions, they have been used as key components in a wide range of applications, including substrate utilization, the synthesis of chemicals, biodegradation and detoxification. There is great interest in tailoring NAD(P)H-dependent oxidoreductases to make them more suitable for particular applications. Here, we review the main properties and classes of NAD(P)H-dependent oxidoreductases, the types of reactions they catalyze, some of the main protein engineering techniques used to modify their properties and some interesting examples of their modification and application.

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On the Enzymatic Activation of NADH

Cited by 105 publications

References 31 publications

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Differential binding of NAD ⁺ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

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On the Enzymatic Activation of NADH

Cited by 105 publications

References 31 publications

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Crystal Structures of Δ1-Piperideine-2-carboxylate/Δ1-Pyrroline-2-carboxylate Reductase Belonging to a New Family of NAD(P)H-dependent Oxidoreductases

Differential binding of NAD + and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

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Differential binding of NAD ⁺ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor