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Information on EC 3.2.2.5 - NAD+ glycohydrolase
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3.2.2.5 NAD+ glycohydrolaseIUBMB Comments
This enzyme catalyses the hydrolysis of NAD+, without associated ADP-ribosyl cyclase activity (unlike the metazoan enzyme EC 3.2.2.6, bifunctional ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase). The enzyme from Group A streptococci has been implicated in the pathogenesis of diseases such as streptococcal toxic shock-like syndrome (STSS) and necrotizing fasciitis. The enzyme from the venom of the snake Agkistrodon acutus also catalyses EC 3.6.1.5, apyrase .
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Word Map
- 3.2.2.5
-
adp-ribosylation
- adp-ribosyltransferase
- streptococcal
- pertussis
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streptolysin
-
ectoenzyme
- aplysia
- diphtheria
-
ribosylation
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exotoxin
- glycosylphosphatidylinositol
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isonicotinic
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glycosylphosphatidylinositol-anchored
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gpi-anchored
- cadp-ribose
- cyclases
- hemoglobinuria
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auto-adp-ribosylation
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calcium-mobilizing
- diphosphoribose
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anti-cd38
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gpi-linked
- nmn
-
bungarus
- medicine
- fasciatus
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nad-binding
- analysis
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holotoxins
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
nadase, cd157, nad glycohydrolase, nad-glycohydrolase, nad+ glycohydrolase, cadpr hydrolase, nad+-glycohydrolase, aa-nadase, smnace, nicotinamide adenine dinucleotide glycohydrolase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(Streptococcus pyogenes NAD+ glycohydrolase)
Acute lymphoblastic leukemia cells antigen CD38
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ADRC
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Antigen BP3
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BP-3 alloantigen
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cADPr hydrolase
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CagL
CD157 antigen
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CD38
CD38 homolog
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CD38H
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Cyclic ADP-ribose hydrolase
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diphosphopyridine nucleosidase
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diphosphopyridine nucleotidase
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DPN hydrolase
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DPNase
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I-19
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Lymphocyte differentiation antigen CD38
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NAD glycohydrolase
NAD hydrolase
NAD nucleosidase
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NAD(+) nucleosidase
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NAD+ catabolizing enzyme
NAD+ glycohydrolase
NAD+-glycohydrolase
NAD-glycohydrolase
NADase
Nga
nicotinamide adenine dinucleotide glycohydrolase
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nicotinamide adenine dinucleotide nucleosidase
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NIM-R5 antigen
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PA0093
PAAR motif containing protein
PFL_6209
SPN
T10
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Tse6
NAD glycohydrolase
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NAD hydrolase
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NADase
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NADase
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multicatalytic enzyme with both NADase and AT(D)Pase activities
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
transglycosylation in mammalian and snake
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NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
the enzyme can also hydrolyse NADP+ to yield phospho-ADP-ribose and nicotinamide, but more slowly
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NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
residues E146, D147, and W125 work collaboratively to facilitate the formation of the Michaelis complex
NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
the polar interactions between E226 and the substrate 2',3'-OH groups are essential for initiating catalysis. S193 has a regulatory role during catalysis and is likely to be involved in intermediate stabilization
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NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
reaction mechanism, and structure-function relationship, overview
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NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
reaction mechanism, and structure-function relationship, overview
NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
SPN shows an ordered uni-bi mechanism, with ADP-ribose being released as a second product. The catalytic mechanism requires an essential glutamic acid, Glu344, to stabilize an oxycarbenium ion intermediate, which subsequently is attacked by a nucleophile, a water molecule
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of N-glycosyl bond
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SYSTEMATIC NAME
IUBMB Comments
NAD+ glycohydrolase
This enzyme catalyses the hydrolysis of NAD+, without associated ADP-ribosyl cyclase activity (unlike the metazoan enzyme EC 3.2.2.6, bifunctional ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase). The enzyme from Group A streptococci has been implicated in the pathogenesis of diseases such as streptococcal toxic shock-like syndrome (STSS) and necrotizing fasciitis. The enzyme from the venom of the snake Agkistrodon acutus also catalyses EC 3.6.1.5, apyrase [3].
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CAS REGISTRY NUMBER
COMMENTARY
9032-65-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-fluoro-NAD+ + H2O
2-fluoro-ADP-ribose + nicotinamide
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in presence of methanol, formation of methanolysis product beta-1''-O-methyl 2-fluoro-ADP-ribose, with a preference for methanolysis over hydrolysis of 100:1
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?
NAD+ + H2O
adenosine + nicotinamide + ?
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solubilized enzyme form sNADase, unusual cleavage reaction, no hydrolysis of the labile quarternary nicotinamide-ribose pyridinium linkage
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?
nicotinamide guanine dinucleotide + H2O
3',5'-cyclic GDP-ribose + GDP-ribose
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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ADP-ribose reacts further with polyarginine, polyhistidine, or polylysine
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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ADP-ribose reacts spontaneously with polyarginine, polyhistidine, or polylysine
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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CD38 is a multifunctional enzyme involved in the degradation of beta-nicotinamide adenine dinucleotide. the beta-nicotinamide adenine dinucleotide/CD38 system may provide new mechanisms in autonomic neurovascular control
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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purified bifunctional enzyme has a ADP-ribosyl cyclase/NAD glycohydrolase ratio of 1/120. In situ cyclase/NAD glycohydrolase ratio measured in seminal plasma is 1/1. Physiological concentrations of zinc present in the seminal fluid, in the range of 0.6 to 4 mM, are responsible for the modulation of the cyclase/NAD glycohydrolase ratio
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?
NAD+ + H2O
ADP-ribose + nicotinamide
substrate binding structure, overview. Catalytically important CD38 residue Thr221 disfavors the cyclizing folding of the substrate, resulting in NADase being the dominant activity
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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low activity in CD38-deficient cell membranes at all developmental stages
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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enzyme contributes to the pathogenicity of group A streptococci, after it is transported into the cytoplasm and membranes of host endothelial cells, by modulation of host cell signalling pathways to inhibit group A streptococci internalization, leading to apoptosis of keratinocytes
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?
NAD+ + H2O
ADP-ribose + nicotinamide
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enzyme contributes to the pathogenicity of group A streptococci, after it is transported into the cytoplasm and membranes of host endothelial cells, by modulation of host cell signalling pathways to inhibit group A streptococci internalization, leading to apoptosis of keratinocytes
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?
NAD+ + H2O
ADPribose + nicotinamide
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137055, 137060, 137063, 137065, 137067, 137068, 137070, 137076, 137077, 137079, 137088, 137089, 137091, 137093, 137095, 137096
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?
NAD+ + H2O
ADPribose + nicotinamide
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NADP+ + H2O
phospho-ADP-ribose + nicotinamide
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NADP+ + H2O
phospho-ADPribose + nicotinamide
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?
additional information
?
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Phe174 in ADP-ribosyl cyclase, ADPRC, is a critical residue in directing the folding of the substrate during the cyclization reaction. Thus, a point mutation of Phe174 to glycine can turn ADPRC from a cyclase toward an NADase, overview
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?
additional information
?
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substrate binding structure of wild-type and mutant enzymes, overview
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?
additional information
?
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alcoholysis of NAD to form O-alkyl-ADP-ribosides, ADP-ribosylation of imidazole derivates
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?
additional information
?
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multifunctional AA-NADase is not only able to cleave the CeN glycosyl bond of NAD to produce ADPR and nicotinamide, but also able to cleave the phosphoanhydride linkages of ATP, ADP and AMP-PNP to yield AMP, overview
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?
additional information
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ATP and ADP are also hydrolyzed by AA-NADase to form ADP and AMP, respectively, theAA-NADase-catalyzed cleavage reaction of NAD is markedly inhibited in the presence of ATP and ADP, overview
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?
additional information
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the multifunctional AA-NADase also shows ADPase activity
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?
additional information
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the multifunctional AA-NADase also shows ADPase activity
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?
additional information
?
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bifunctional enzyme ADP-ribose cyclase/NAD glycohydrolase, enzyme activities are regulated by zinc, enzyme is capable of both synthesis and hydrolysis of cADP-ribose
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?
additional information
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bifunctional enzyme ADP-ribose cyclase/NAD glycohydrolase, enzyme is capable of both synthesis and hydrolysis of cADP-ribose
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?
additional information
?
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enzyme plays a crucial role in neutrophil diapedesis. Its ligation with specific monoclonal antibodies both on neutrophils or endothelial cells results in altered neutrophil movement on the apical surface of endothelium and, ultimately, in loss of diapedesis. Following CD157 ligation, neutrophils appear disoriented, meandering toward junctions where they eventually stop without transmigrating
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?
additional information
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the ADP-ribosyl cyclase activity shows identical properties and is inseparable, thus the enzyme is bifunctional one
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?
additional information
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CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins
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?
additional information
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CD38 rather than poly-ADP-ribose polymerase PARP-1, is an important source of ADP-ribose in mouse neutrophils and dendritic cells that use ADP-ribose as a secong messenger. ADP-ribose controls calcium influx and chemotaxis when cells are activated through chemokine receptors that rely on CD38 and cyclic ADP-ribose for activity
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?
additional information
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enzyme-mediated inhibition of osteoclastogenesis is related to its NADase activity, not its ADPribosyl cyclase activity
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additional information
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nicotinamide and ADP-ribose are the only detectable products, no cyclization is found, i.e. no reaction of EC 3.2.2.6
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?
additional information
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nicotinamide and ADP-ribose are the only detectable products, no cyclization is found, i.e. no reaction of EC 3.2.2.6
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?
additional information
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enzyme is involved in regulation of mitogen-stimulated T-cell proliferation by inhibition via NAD+ and ADP-ribose, not nicotinamide
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?
additional information
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NADP is not cleaved by chromatin NADase
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?
additional information
?
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streptolysin and NAD+ -glycohydrolase interact functionally as a compound signaling toxin. When Streptococcus pyogenes is bound to the surface of epithelial cells in vitro, streptolysin forms pores in the cell membrane and delivers NADase to the epithelial cell cytoplasm. In vitro, intoxication of keratinocytes with NADase is associated with cytotoxic effects and induction of apoptosis. NADase and streptolysin together enhance Streptococcus pyogenes virulence in vivo
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?
additional information
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the capacity of NADase to enhance streptolysin O-mediated cytotoxicity is not due to a direct effect on pore formation but rather due to depletion of cellular NAD+ and ATP
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?
additional information
?
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SPN is specific for beta-NAD+ glycohydrolase activity, and does not show ADP-ribosyl cyclase and ADP-ribosyltransferase activities, overview. SPN is unable to catalyze cyclic ADPR hydrolysis, and cannot catalyze methanolysis or transglycosidation
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?
additional information
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lack of ADP-ribosyltransferase activity of the enzyme
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified