Enzymes
UniProtKB help_outline | 910 proteins |
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- Name help_outline 1,6-dihydro-β-NAD Identifier CHEBI:88140 Charge -2 Formula C21H27N7O14P2 InChIKeyhelp_outline QVQHBKNZCMZBKP-NNYOXOHSSA-L SMILEShelp_outline N1(C2=C(C(=NC=N2)N)N=C1)[C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C=CC5)C(=O)N)[C@@H]([C@@H]4O)O)(=O)[O-])(=O)[O-])[C@H]([C@H]3O)O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,727 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O2 Identifier CHEBI:16240 (CAS: 7722-84-1) help_outline Charge 0 Formula H2O2 InChIKeyhelp_outline MHAJPDPJQMAIIY-UHFFFAOYSA-N SMILEShelp_outline [H]OO[H] 2D coordinates Mol file for the small molecule Search links Involved in 452 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,190 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:47996 | RHEA:47997 | RHEA:47998 | RHEA:47999 | |
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Publications
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Bacterial renalase: structure and kinetics of an enzyme with 2- and 6-dihydro-beta-NAD(P) oxidase activity from Pseudomonas phaseolicola.
Hoag M.R., Roman J., Beaupre B.A., Silvaggi N.R., Moran G.R.
Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of β-NAD(P) ... >> More
Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of β-NAD(P)H as substrates for renalase (Beaupre, B. A. et al. (2015) Biochemistry, 54, 795-806). These molecules carry the hydride equivalent on the 2 or 6 position of the nicotinamide base and presumably arise in nonspecific redox reactions of nicotinamide dinucleotides. Renalase serves to rapidly oxidize these isomers to form β-NAD(P)⁺ and then pass the electrons to dioxygen, forming H₂O₂. We have also shown that these substrate molecules are highly inhibitory to dehydrogenase enzymes and thus have proposed an intracellular metabolic role for this enzyme. Here, we identify a renalase from an organism without a circulatory system. This bacterial form of renalase has the same substrate specificity profile as that of human renalase but, in terms of binding constant (K(d)), shows a marked preference for substrates derived from β-NAD⁺. 2-dihydroNAD(P) substrates reduce the enzyme with rate constants (k(red)) that greatly exceed those for 6-dihydroNAD(P) substrates. Taken together, k(red)/K(d) values indicate a minimum 20-fold preference for 2DHNAD. We also offer the first structures of a renalase in complex with catalytically relevant ligands β-NAD⁺ and β-NADH (the latter being an analogue of the substrate(s)). These structures show potential electrostatic repulsion interactions with the product and a unique binding orientation for the substrate nicotinamide base that is consistent with the identified activity. << Less
Biochemistry 54:3791-3802(2015) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Metabolic function for human renalase: oxidation of isomeric forms of beta-NAD(P)H that are inhibitory to primary metabolism.
Beaupre B.A., Hoag M.R., Roman J., Foersterling F.H., Moran G.R.
Renalase is a recently identified flavoprotein that has been associated with numerous physiological maladies. There remains a prevailing belief that renalase functions as a hormone, imparting an influence on vascular tone and heart rate by oxidizing circulating catecholamines, chiefly epinephrine. ... >> More
Renalase is a recently identified flavoprotein that has been associated with numerous physiological maladies. There remains a prevailing belief that renalase functions as a hormone, imparting an influence on vascular tone and heart rate by oxidizing circulating catecholamines, chiefly epinephrine. This activity, however, has not been convincingly demonstrated in vitro, nor has the stoichiometry of this transformation been shown. In prior work we demonstrated that renalase induced rapid oxidation of low-level contaminants of β-NAD(P)H solutions ( Beaupre, B. A. et al. (2013) Biochemistry 52 , 8929 - 8937 ; Beaupre, B. A. et al. (2013) J. Am. Chem. Soc . 135 , 13980 - 13987 ). Slow aqueous speciation of β-NAD(P)H resulted in the production of renalase substrate molecules whose spectrophotometric characteristics and equilibrium fractional accumulation closely matched those reported for α-anomers of NAD(P)H. The fleeting nature of these substrates precluded structural assignment. Here we structurally assign and identify two substrates for renalase. These molecules are 2- and 6-dihydroNAD(P), isomeric forms of β-NAD(P)H that arise either by nonspecific reduction of β-NAD(P)(+) or by tautomerization of β-NAD(P)H (4-dihydroNAD(P)). The pure preparations of these molecules induce rapid reduction of the renalase flavin cofactor (230 s(-1) for 6-dihydroNAD, 850 s(-1) for 2-dihydroNAD) but bind only a few fold more tightly than β-NADH. We also show that 2- and 6-dihydroNAD(P) are potent inhibitors of primary metabolism dehydrogenases and therefore conclude that the metabolic function of renalase is to oxidize these isomeric NAD(P)H molecules to β-NAD(P)(+), eliminating the threat they pose to normal respiratory activity. << Less
Biochemistry 54:795-806(2015) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Renalase is an alpha-NAD(P)H oxidase/anomerase.
Beaupre B.A., Carmichael B.R., Hoag M.R., Shah D.D., Moran G.R.
Renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate. Since its discovery in 2005, renalase has been the subject of conjecture pertaining to its catalytic function. While it has been widely reported that renalase is the th ... >> More
Renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate. Since its discovery in 2005, renalase has been the subject of conjecture pertaining to its catalytic function. While it has been widely reported that renalase is the third monoamine oxidase (monoamine oxidase C) that oxidizes circulating catecholamines such as epinephrine, there has been no convincing demonstration of this catalysis in vitro. Renalase is a flavoprotein whose structural topology is similar to known oxidases, lysine demethylases, and monooxygenases, but its active site bears no resemblance to that of any known flavoprotein. We have identified the catalytic activity of renalase as an α-NAD(P)H oxidase/anomerase, whereby low equilibrium concentrations of the α-anomer of NADPH and NADH initiate rapid reduction of the renalase flavin cofactor. The reduced cofactor then reacts with dioxygen to form hydrogen peroxide and releases nicotinamide dinucleotide product in the β-form. These processes yield an apparent turnover number (0.5 s(-1) in atmospheric dioxygen) that is at least 2 orders of magnitude more rapid than any reported activity with catechol neurotransmitters. This highly novel activity is the first demonstration of a role for naturally occurring α-NAD(P)H anomers in mammalian physiology and the first report of a flavoprotein catalyzing an epimerization reaction. << Less
J. Am. Chem. Soc. 135:13980-13987(2013) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.