NADP‐Dependent enzymes. I: Conserved stereochemistry of cofactor binding

  title={NADP‐Dependent enzymes. I: Conserved stereochemistry of cofactor binding},
  author={Oliviero Carugo and Patrick Argos},
  journal={Proteins: Structure},
The ubiquitous redox cofactors nicotinamide adenine dinucleotides [NAD and NADP] are very similar molecules, despite their participation in substantially different biochemical processes. NADP differs from NAD in only the presence of an additional phosphate group esterified to the 2′‐hydroxyl group of the ribose at the adenine end and yet NADP is confined with few exceptions to the reactions of reductive biosynthesis, whereas NAD is used almost exclusively in oxidative degradations. The… 
NADP‐Dependent enzymes. II: Evolution of the mono‐ and dinucleotide binding domains
There is evidence to postulate that evolutionary pathways for NAD(P)‐dependent enzymes are both divergent and convergent and nearly all combinations of similarity/dissimilarity in overall fold, cofactor conformation, and cofactor binding pocket structural characteristics for each enzyme pair examined are possible.
Linking distinct conformations of nicotinamide adenine dinucleotide with protein fold/function.
The various distinct enzyme-bound NAD(P) conformations and their correlation with the respective protein fold and function are elucidated using hierarchical clustering methods to provide useful guidelines in the design of inhibitors/activators of NAD( P)-dependent enzymes that are therapeutic targets.
Structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase from Synechococcus PCC7942 complexed with NADP.
The crystal structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (NADP-GAPDH) from Synechococcus PCC 7942 (S. 7942) in complex with NADP was solved by molecular replacement and
NADP+ and NAD+ binding to the dual coenzyme specific enzyme Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase: different interdomain hinge angles are seen in different binary and ternary complexes.
The reduced coenzymes NADH and NADPH only differ by one phosphate, but in the cell NADH provides reducing power for catabolism while NADPH is utilized in biosynthetic pathways. Enzymes almost
Nadp+-dependent formate dehydrogenase: a review
To switch the coenzyme preference ofFDHs or to find the native NADP+-dependent FDHs will be the hot topics in bioengineering until finding a feasible regenerator, so this study will be a useful guide to get a pathway for designing or discovering novel NADP+.
The Negative Transcriptional Regulator NmrA Discriminates between Oxidized and Reduced Dinucleotides*
The structure of NmrA in a complex with NADP+ reveals how repositioning a His-37 side chain allows the different conformations of NAD+ and NADp+ to be accommodated, and modeling NAD(P)H into NMRA indicated that steric clashes, attenuation of electrostatic interactions, and loss of aromatic ring stacking can explain the differing affinities of NAD( P)+/NAD( P)H.


An aspartate residue in yeast alcohol dehydrogenase I determines the specificity for coenzyme.
The D223G enzyme bound and reduced NAD+ and NADP+ equally well, but, relative to wild-type enzyme, the dissociation constant for NAD+ was increased 17-fold, and the reactivity (V/K) on ethanol was decreased to 1%.
NAD-binding domains of dehydrogenases.
  • A. Lesk
  • Biology
    Current opinion in structural biology
  • 1995
Crystallographic investigations of nicotinamide adenine dinucleotide binding to horse liver alcohol dehydrogenase.
The binding of NAD to liver alcohol dehydrogenase has been studied in four different ternary complexes by using crystallographic methods, and the overall conformation of the NAD molecule is similar to that observed for other dehydrogenases, but differs in details.
Structure of isocitrate dehydrogenase with isocitrate, nicotinamide adenine dinucleotide phosphate, and calcium at 2.5-A resolution: a pseudo-Michaelis ternary complex.
The structure of isocitrate dehydrogenase (IDH) with a bound complex of isOCitrate, NADP+, and Ca2+ was solved at 2.5-A resolution and compared by difference mapping against previously determined enzymatic complexes to demonstrate stereospecificity of the enzyme-catalyzed reaction.
Subunit assembly and active site location in the structure of glutamate dehydrogenase
The three‐dimensional crystal structure of the NAD+‐linked glutamate dehydrogenase from Clostridium symbiosum has been solved to 1.96 Å resolution by a combination of isomorphous replacement and
High resolution structures of holo and apo formate dehydrogenase.
Three-dimensional crystal structures of holo (ternary complex enzyme-NAD-azide) and apo NAD-dependent dimeric formate dehydrogenase (FDH) from the methylotrophic bacterium Pseudomonas sp. 101 have
Characteristics of short-chain alcohol dehydrogenases and related enzymes.
Comparisons of the different enzymes reveal large homologous parts, with clustered similarities indicating regions of special functional/structural importance, and suggest the possibility of related mechanisms and domain properties for different members of the short-chain family.
Redesign of the coenzyme specificity of a dehydrogenase by protein engineering
Directed mutagenesis and molecular modelling have been used to identify a set of amino-acid side chains in glutathione reductase that confer specificity for the coenzyme NADP+. Systematic replacement