title: Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair.
abstract: The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. We report the molecular identification of the eukaryotic dehydratase that repairs these nucleotides and show that this enzyme (Carkd in mammals, YKL151C in yeast) catalyzes the dehydration of the S form of NADHX and NADPHX, at the expense of ATP, which is converted to ADP. Surprisingly, the Escherichia coli homolog, YjeF, a bidomain protein, catalyzes a similar reaction, but using ADP instead of ATP. The latter reaction is ascribable to the C-terminal domain of YjeF. This represents an unprecedented example of orthologous enzymes using either ADP or ATP as phosphoryl donor. We also show that eukaryotic proteins homologous to the N-terminal domain of YjeF (apolipoprotein A-1-binding protein (AIBP) in mammals, YNL200C in yeast) catalyze the epimerization of the S and R forms of NAD(P)HX, thereby allowing, in conjunction with the energy-dependent dehydratase, the repair of both epimers of NAD(P)HX. Both enzymes are very widespread in eukaryotes, prokaryotes, and archaea, which together with the ADP dependence of the dehydratase in some species indicates the ancient origin of this repair system.
authors: WELBIO and the Laboratory of Physiological Chemistry, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium.
authors: Alexandre Y
authors: AY
authors: Marbaix
authors: WELBIO and the Laboratory of Physiological Chemistry, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium.
authors: Gaëtane
authors: G
authors: Noël
authors: WELBIO and the Laboratory of Physiological Chemistry, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium.
authors: Aline M
authors: AM
authors: Detroux
authors: Hormone and Metabolic Research Unit, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium.
authors: Didier
authors: D
authors: Vertommen
authors: WELBIO and the Laboratory of Physiological Chemistry, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium. Electronic address: emile.vanschaftingen@uclouvain.be.
authors: Emile
authors: E
authors: Van Schaftingen
authors: WELBIO and the Laboratory of Physiological Chemistry, de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium. Electronic address: carole.linster@uclouvain.be.
authors: Carole L
authors: CL
authors: Linster
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006836:Hydro-Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009243:NAD / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009249:NADP / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029968:Escherichia coli Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486302:RCN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D009249:NADP; C058017:6-hydroxy-1,4,5,6-tetrahydronicotinamide adenine dinucleotide; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006836:Hydro-Lyases