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Enzyme Nomenclature
Information on EC 3.2.2.5 - NAD+ glycohydrolase
for references in articles please use BRENDA:EC3.2.2.5
Word Map on EC 3.2.2.5
- 3.2.2.5
-
adp-ribosylation
-
adp-ribosyltransferase
- streptococcal
- pertussis
-
streptolysin
-
ectoenzyme
- aplysia
- glycosylphosphatidylinositol
-
gpi-anchored
-
exotoxin
- diphosphoribose
- diphtheria
-
ribosylation
-
choleragen
-
gpi-linked
-
auto-adp-ribosylation
-
isonicotinic
- nmn
- hemoglobinuria
-
anti-cd38
-
bungarus
-
holotoxins
- agkistrodon
- cadp-ribose
-
calcium-mobilizing
-
ca2+-mobilizing
-
ryanodine
-
glycosylphosphatidylinositol-anchored
-
nad-binding
-
mono-adp-ribosylation
- fasciatus
- medicine
- analysis
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
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EC NUMBER 
COMMENTARY 
3.2.2.5
-
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RECOMMENDED NAME
GeneOntology No.
NAD+ glycohydrolase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NAD+ + H2O = ADP-D-ribose + nicotinamide
transglycosylation in mammalian and snake
-
-
-
NAD+ + H2O = ADP-D-ribose + nicotinamide
the enzyme can also hydrolyse NADP+ to yield phospho-ADP-ribose and nicotinamide, but more slowly
-
NAD+ + H2O = ADP-D-ribose + nicotinamide
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
-
NAD+ + H2O = ADP-D-ribose + nicotinamide
residues E146, D147, and W125 work collaboratively to facilitate the formation of the Michaelis complex
NAD+ + H2O = ADP-D-ribose + nicotinamide
reaction mechanism, and structure-function relationship, overview
-
NAD+ + H2O = ADP-D-ribose + nicotinamide
reaction mechanism, and structure-function relationship, overview
NAD+ + H2O = ADP-D-ribose + nicotinamide
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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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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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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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
diverse strains, e.g. strain SF370, of low and high NADase activity, as isolates taken from streptococcal toxic shock-like syndrome, STSS, patients, gene nga
-
-
isolated from Euprymna scolopes light organ, genes hvnA and hvnB
SwissProt
isolated from Euprymna scolopes light organ, genes hvnA and hvnB
SwissProt
isolated from Euprymna scolopes, genes hvnA and hvnB
SwissProt
bifunctional adenosine 5-diphosphate ribosyl cyclase/NAD+ glycohydrolase
-
-
the extracellular domain of the leukocyte single transmembrane cell surface antigen CD38 shows NADase activity
-
-
-
-
-
presence of clindamycin during early log-phase growth results in increased production of enzyme. Administration of clindamycin at mid log-phase growth inhibits the production of most types of proteins
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
the enzyme shows significant structural and functional analogy to the members of the CD38/ADP-ribosyl cyclase family but a lack of ADP-ribosyl cyclase activity that might be ascribed to subtle changes in its active site. In sharp contrast with mammalian CD38, the signature Glu124 is as critical as Glu202 for catalysis by the parasite enzyme. Sequence comparisons
evolution
-
the enzyme is evolving and has diverged into NAD+ glycohydrolase-inactive variants that correlate with tissue tropism. Of a total 454 amino acids, the activity-deficient variants differ at only nine highly conserved positions
evolution
-
the enzyme is evolving and has diverged into NAD+ glycohydrolase-inactive variants that correlate with tissue tropism. Of a total 454 amino acids, the activity-deficient variants differ at only nine highly conserved positions
-
malfunction
-
the enzyme represents one major virulent exoprotein in the streptococcal toxic shock syndrome, overview
malfunction
-
shRNA-mediated knockdown of the NADase in bone marrow cells results in a reduction of erythroid colony formation and an increase in NAD level, and treatment of the bone marrow cells with NAD, nicotinamide, or nicotinamide riboside, which induce an increase in NAD content, results in a significant decrease in erythroid progenitors
malfunction
-
shRNA-mediated knockdown of the NADase in bone marrow cells results in a reduction of erythroid colony formation and an increase in NAD level, and treatment of the bone marrow cells with NAD, nicotinamide, or nicotinamide riboside, which induce an increase in NAD content, results in a significant decrease in erythroid progenitors
-
physiological function
-
NADase is important for the virulence of Streptococcus pyogenes in vivo, is important in severe invasive diseases, and is the potential target to suppress the virulence
physiological function
-
SPN is a virulence factor that is implicated in contributing to the pathogenesis of severe infections, e.g. of the throat, leading to pharyngitis, or the skin, leading to impetigo. NADase activity does not correlate with invasive disease, but is associated with tissue tropism. The ability to cause infection at both the pharynx and the skin is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin is associated with NADase-inactive SPN
physiological function
CD38 has multiple activities, i.e. in cyclic ADP-ribose, cADPR, production and degradation, as well as NAD hydrolysis as NADase
physiological function
-
the enzyme is secreted from the bacterial cell and translocated into the host cell cytosol where it contributes to cell death
physiological function
-
the enzyme may play a critical role in regulating erythropoiesis of hematopoietic stem cells by modulating intracellular NAD+
physiological function
Q7CFI6;
the enzyme is one of the virulence factors produced by Streptococcus pyogenes, which injects the enzyme into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. For the export of the enzyme through the cell envelope, the intracellular complex with inhibitor IFN must be dissociated
physiological function
-
expression of toxin streptolysin O is associated with prolonged intracellular survival of the bacterium in human oropharyngeal keratinocytes, the predominant cell type of the pharyngeal epithelium, co-toxin NADase is required for this effect. Production of streptolysin S can mediate targeting of GAS to autophagosomes in the absence of streptolysin O, a process accompanied by galectin 8 binding to damaged Streptococcus pyogenes-containing endosomes. Maturation of Streptococcus pyogenes-containing autophagosome-like vacuoles to degradative autolysosomes is prevented by streptolysin O pore-formation and by streptolysin O-mediated translocation of enzymatically active NADase into the keratinocyte cytosol. Coordinated action of streptolysin O and NADase prevent maturation of GAS-containing autophagosomes, thereby prolonging Streptococcus pyogenes intracellular survival, overview. The activity of NADase to block autophagic killing of Streptococcus pyogenes in pharyngeal cells may contribute to pharyngitis treatment failure, relapse, and chronic carriage caused by the pathogen
physiological function
-
high enzyme levels in serum are associated with a poor prognosis in patients with colorectal cancer
physiological function
-
the enzyme may play a critical role in regulating erythropoiesis of hematopoietic stem cells by modulating intracellular NAD+
-
physiological function
-
the enzyme is secreted from the bacterial cell and translocated into the host cell cytosol where it contributes to cell death
-
additional information
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models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD+ glycohydrolase-active and -inactive subtypes
additional information
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structural determinants for the functional evolution from a cyclase to a hydrolase, overview
additional information
structural determinants for the functional evolution from a cyclase to a hydrolase, overview
additional information
-
the Gram-positive pathogen Streptococcus pyogenes injects a beta-NAD+-glycohydrolase into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway, where SPN accelerates the death of the host cell
additional information
three dimensional homology modeling of the enzyme, very important role of Glu202 and of the hydrophobic domains overwhelmingly in the efficiency of the nicotinamide-ribosyl bond cleavage step. The nicotinamide-ribosyl bond is cleaved upon the first step of catalysis and is surrounded by three hydrophobic side chains Leu123, Tyr172 and Phe102
additional information
-
no one single residue can account for the inability of the deficient variants to cleave the glycosidic bond of beta-NAD+ into nicotinamide and ADP-ribose. Reciprocal changes at 3 specific residues are required to both abolish activity of the proficient version and restore full activity to the deficient variant
additional information
-
the catalytic glutamine 218 of NADase is a crucial residue for NADase activity
additional information
-
the catalytic glutamine 218 of NADase is a crucial residue for NADase activity
-
additional information
-
no one single residue can account for the inability of the deficient variants to cleave the glycosidic bond of beta-NAD+ into nicotinamide and ADP-ribose. Reciprocal changes at 3 specific residues are required to both abolish activity of the proficient version and restore full activity to the deficient variant
-
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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
-
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
-
-
?
NAD+ + H2O
adenosine + nicotinamide
-
solubilized enzyme form sNADase, unusual cleavage reaction, no hydrolysis of the labile quarternary nicotinamide-ribose pyridinium linkage
-
-
?
nicotinamide guanine dinucleotide + H2O
3',5'-cyclic GDP-ribose + GDP-ribose
-
-
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
ADP-ribose reacts further with polyarginine, polyhistidine, or polylysine
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
ADP-ribose reacts spontaneously with polyarginine, polyhistidine, or polylysine
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
ADP-ribose reacts further with polyarginine, polyhistidine, or polylysine
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
ADP-ribose reacts spontaneously with polyarginine, polyhistidine, or polylysine
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
low activity in CD38-deficient cell membranes at all developmental stages
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
-
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
?
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
?
additional information
?
-
-
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
-
-
-
additional information
?
-
-
substrate binding structure of wild-type and mutant enzymes, overview
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-
-
additional information
?
-
-
alcoholysis of NAD to form O-alkyl-ADP-ribosides, ADP-ribosylation of imidazole derivates
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
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the multifunctional AA-NADase also shows ADPase activity
-
-
-
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
-
-
-
additional information
?
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bifunctional enzyme ADP-ribose cyclase/NAD glycohydrolase, enzyme is capable of both synthesis and hydrolysis of cADP-ribose
-
-
-
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
-
-
-
additional information
?
-
-
the ADP-ribosyl cyclase activity shows identical properties and is inseparable, thus the enzyme is bifunctional one
-
-
-
additional information
?
-
-
CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
enzyme-mediated inhibition of osteoclastogenesis is related to its NADase activity, not its ADPribosyl cyclase activity
-
-
-
additional information
?
-
-
enzyme is involved in regulation of mitogen-stimulated T-cell proliferation by inhibition via NAD+ and ADP-ribose, not nicotinamide
-
-
-
additional information
?
-
-
NADP is not cleaved by chromatin NADase
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
Q7CFI6;
lack of ADP-ribosyltransferase activity of the enzyme
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADP-ribose + nicotinamide
-
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
-
-
?
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
-
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
?
NAD+ + H2O
ADPribose + nicotinamide
-
-
-
-
?
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
bifunctional enzyme ADP-ribose cyclase/NAD glycohydrolase, enzyme activities are regulated by zinc, enzyme is capable of both synthesis and hydrolysis of cADP-ribose
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
enzyme-mediated inhibition of osteoclastogenesis is related to its NADase activity, not its ADPribosyl cyclase activity
-
-
-
additional information
?
-
-
enzyme is involved in regulation of mitogen-stimulated T-cell proliferation by inhibition via NAD+ and ADP-ribose, not nicotinamide
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
AA-NADase has one strong and two weak Co2+ binding sites; the enzyme has one strong and two weak Co2+ binding sites
Cu2+
Mn2+
-
AA-NADase has one Mn2+ binding site; the enzyme has one Mn2+ binding site
Ni2+
-
AA-NADase has two strong and six weak Ni2+ binding sites; the enzyme has two strong and six weak Ni2+ binding sites
Zinc
-
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
Zn2+
additional information
Cu2+
-
among all identified NADases, only AA-NADase contains Cu2+ and has six disulfide-bond linkages between two peptide chains. The binding of Cu2þ ions to AA-NADase is reversible, overview
Cu2+
-
among all identified NADases, only AA-NADase contains Cu2+ and has six disulfide-bond linkages between two peptide chains
Cu2+
-
although Cu2+ ions are important for catalyzing the hydrolysis of NAD, they are also able to inhibit its NADase activity in a concentration-dependent manner, Cu2+ ions in low-affinity binding sites inhibit its NADase activity. AA-NADase has two classes of Cu2+ binding sites, one activator site with high affinity and approximately six inhibitor sites with low affinity. Cu2+ ions function as a switch for its NADase activity.; the enzyme contains Cu2+ ions that are essential for its multicatalytic activity. The enzyme has two classes of Cu2+ binding sites, one activator site with high affinity and approximately six inhibitor sites with low affinity. Both NADase and ADPase activities of the enzyme do not have an absolute requirement for Cu2+ and may be replaced by Zn2+ > Mn2+ > Cu2+/Co2+ > Ni2+
Zn2+
-
apo-AA-NADase can recover its NADase and ADPase activities in the presence of 1 mM Zn2+, which is inhibited by tris(2-carboxyethyl)phosphine
Zn2+
-
AA-NADase has one Zn2+ binding site; the enzyme has one Zn2+ binding site
Zn2+
-
stimulates the cyclase activity, inhibits the NAD glycohydrolase activity, zinc has a regulatory function at physiological concentrations of 0.6-4 mM, responsible for modulation of the ADP-ribose cyclase/NAD glycohydrolase activity ratio of the bifunctional enzyme in zinc-rich seminal plasma to 1:3 in situ, with the purified enzyme in absence of zinc the ratio is 1:110-120, in presence of Zn2+ it is 1:2-3, mechanism
additional information
-
no absolute requirement for metal ions, metal ion binding affinities in descending order: Cu2+ , Ni2+, Mn2+, Co2+, and Zn2+. Enzyme-metal ion interaction analysis by equilibrium dialysis, isothermal titration calorimetry, fluorescence, circular dichroism, dynamic light scattering and HPLC, overview
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ADP-(2-deoxy-2-fluoro-D-arabinose)
the NAD analogue forms a covalent adduct after nicotinamide cleavage, resulting in inhibition of the enzyme activity, binding structure, overview
ADP-(2-deoxy-2-fluoro-D-ribose)
the NAD analogue forms a covalent adduct after nicotinamide cleavage, resulting in inhibition of the enzyme activity, binding structure, overview
beta-NAD+
-
substrate inhibition, mediated by ADP-ribosylation, partially reversible by arginine or histidine, inhibits apoptosis in vivo
Cu2+
-
the enzyme has two classes of Cu2+ binding sites, one activator site with high affinity and approximately six inhibitor sites with low affinity
dithiothreitol
-
inhibits both NADase and ADPase activities through the reduction of Cu(II) to Cu(I) and the cleavage of disulfide-bonds in AA-NADase
glutathione
-
inhibits both NADase and ADPase activities through the reduction of Cu(II) to Cu(I) and the cleavage of disulfide-bonds in AA-NADase
GT1b
-
exogenous ganglioside, inhibition in vivo, needs to be incorporated into the cell to inhibit CD38, preferably cis interaction, i.e. CD38 and GT1b are located on the same cell, the tandem sialic acid residues linked to the internal galactose of the gangliotetraose core are crucial to the inhibition
hydroxylamine
inhibits the reaction between ADP-ribose and polypeptides
L-ascorbate
-
inhibits AA-NADase on both NADase and ADPase activities through the reduction of Cu(II) in AA-NADase to Cu(I)
monoclonal antibody CS/2
-
inhibits the NAD+ glycohydolase activity of both the isolated extracellular domain of CD38 and cell-surface CD38, non-competitive. No effect on cyclase activity of enzyme
-
Streptococcal NAD glycohydrolase inhibitor
Q7CFI6;
the ifs gene, or SpyM3_0129, encodes an endogenous competitive inhibitor for the enzyme. IFS is localized intracellularly and forms a complex with the enzyme. This intracellular complex must be dissociated during export through the cell envelope. The interface between SPNct and IFS is highly rich in water molecules, binding structure, overview
-
streptococcal NADase inhibitor
-
161 amino acids, MW 18800 Da, thermostable. Monomeric NADase and the streptococcal NADase inhibitor rapidly form in vitro a stable heterodimer complex in the ratio 1.1, resulting in complete suppression of the hydrolase activity. The inhibitor protein, coexpressed and complexed with NADase, may protect the producer cocci from exhausion of NAD
-
tris(2-carboxyethyl)phosphine
-
TCEP, inhibits both NADase and ADPase activities through the reduction of Cu(II) to Cu(I) and the cleavage of disulfide-bonds in AA-NADase
protein IFS
-
an endogenous NADase inhibitor, encoded by gene ifs, and localized in the cytoplasm. The NADase precursor exists as an inactive complex with IFS
-
Zn2+
-
stimulates the cyclase activity, inhibits the NAD glycohydrolase activity, zinc has a regulatory function at physiological concentrations of 0.6-4 mM, responsible for modulation of the ADP-ribose cyclase/NAD glycohydrolase activity ratio of the bifunctional enzyme in zinc-rich seminal plasma to 1:3 in situ, with the purified enzyme in absence of zinc the ratio is 1:110-120, in presence of Zn2+ it is 1:2-3, mechanism
additional information
-
N1-alkylnicotinamide chlorides, n-alkylphosphates, aliphatic carboxylic acids, other pyridine bases other than nicotinamide, certain pyridine dinucleotides
-
additional information
-
variety of pyridine bases, pyridine nucleotides
-
additional information
-
aliphatic amines and carboxylic acids are noncompetitive inhibitors
-
additional information
-
phosphatidylinositol-specific phospholipase C removes the GPI-anchored enzyme from the T-cell surface, not the non-GPI-anchored activity like with ART2- T-cells
-
additional information
-
not inhibited by rac-catechin, piceatannol, trans-resveratrol, praziquantel, cucurmin, chloroquine, mefloquine, Cibacron Blue 3GA, PJ-34, and 1,8-naphthalimide
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dioxane
-
up to 0.05 mM dioxane produces the more active monomeric form of the NADase
guanosine 5'-O-(3-thiotriphosphate)
-
enzyme may be regulated by a G protein-dependent mechanism
monoclonal antibody clone 90
-
stimulates the NAD+ glycohydrolase activity of the isolated extracellular domain of CD38, little effect on cell-surface CD38. No effect on cyclase activity of enzyme
-
additional information
-
increase in activity ba Triton X-100 treatment due to solubilization from the cells
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Michaelis-Menten kinetics, and kinetic analysis
-
additional information
additional information
-
kinetics and thermodynamics in presence of different metal ions, overview
-
additional information
additional information
steady-state kinetics
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
inhibition kinetics, overview
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0023
cyanidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.006
delphinidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0099
diosmetinidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0064
fisetinidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0082
kuromanin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0084
luteolin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0059
luteolinidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.008
malvidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.022
myricetin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0044
pelargonidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0056
peonidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0378
petunidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0013
quercetagetin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0061
quercetagetinidin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0039
quercetin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0195
rac-taxifolin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.0058
robinetin
Schistosoma mansoni;
-
at 37°C in 10 mM potassium phosphate buffer, pH 7.4, containing 0.05% (w/v) emulphogen
0.42
tris(2-carboxyethyl)phosphine
Deinagkistrodon acutus;
-
pH 7.4, 37°C, inhibition of the NADase activity
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
activities of hydrolysis of NAD, ATP, ADP, and and AMP-PNP, overview
additional information
-
simple and fast fluorescence-based assay method to evaluate the NAD+ glycohydrolase activity of cell-permeable C3 proteins
additional information
-
virulence/Mortality to mice of GAS isolates with different NADase activity, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
6.5 - 7
7.2
7.3
7.4
7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
40
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
TRAP(+) osteoclast formation is inhibitied by exogenous addition of enzyme or of ADPribose
-
enzyme level and ADP-ribosylation is significantly higher in patients and are correlated with tumour stage
-
from bone marrow. Tumor necrosis factor alpha upregulates CD38. Induced CD38 expression enhances inflammatory gene expression by decreasing ERK1/2 phosphorylation and increasing NF kappaB activation. It negatively affects the expression of osteoclast markers. CD38 may reduce osteoclastogenesis and increase inflammatory gene induction by decreasing cellular histone deacetylase activity
-
CD38 is localized in or on sympathetic nerve terminals of this blood vessel
-
CD38 is localized in or on sympathetic nerve terminals of this blood vessel
-
high enzyme levels in serum are associated with a poor prognosis in patients with colorectal cancer
-
enzyme is partially GPI-anchored, T-cell lacking ADP-ribosyltransferase activity
additional information
-
neonatal and adult brain. Brain content of cyclic ADP-ribose is independent of the presence of enzyme
-
erythrocytes from cancer patients exhibit up to fivefold higher NAD+ glycohydrolase activities than control erythrocytes from normal subjects
additional information
-
not in muscle, heart, brain, kidney, spleen, liver, lung, and testis
additional information
-
not in muscle, heart, brain, kidney, spleen, liver, lung, and testis
-
additional information
-
streptolysin O (a cholesterol-dependent cytolysin) produced by Streptococcus pyogenes mediates the translocation of Streptococcus pyogenes NAD glycohydrolase into human epithelial cells
additional information
-
the Gram-positive pathogen Streptococcus pyogenes injects a beta-NAD+-glycohydrolase into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway
additional information
-
sterptolysin O-mediated translocation of the enzyme into human host keratinocytes
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
NADase is a glycosylated, glycosylphosphatidylinositol-anchored cell surface protein
-
NADase is a glycosylated, glycosylphosphatidylinositol-anchored cell surface protein
-
-
the enzyme is secreted from the bacterial cell and translocated into the host epithelial cell cytosol by a process termed cytolysin-mediated translocation. Translocation across the host cell membrane requires a second streptococcal protein, the cholesterol-dependent cytolysin streptolysin O. Both active and inactive SPN haplotypes undergo cytolysin-mediated translocation.The enzyme has multiple domains, including an N-terminal domain required for translocation and a C-terminal enzymatic domain
-
-
the enzyme is secreted from the bacterial cell and translocated into the host epithelial cell cytosol by a process termed cytolysin-mediated translocation. Translocation across the host cell membrane requires a second streptococcal protein, the cholesterol-dependent cytolysin streptolysin O. Both active and inactive SPN haplotypes undergo cytolysin-mediated translocation.The enzyme has multiple domains, including an N-terminal domain required for translocation and a C-terminal enzymatic domain
-
-
-
transmembrane protein with a catalytically active extracellular domain
-
no solubilization by phosphatidylinositol-specific phospholipase C or 0.5 M KCl, but by Triton X-100
-
appropriate assembly of CD38 homodimers may play an important role in stabilizing CD38 on the plasma membrane of B cells
-
localized to plasma membrane but not to intracellular membrane
additional information
Q7CFI6;
the enzyme is injected across the host cell membrane into the cytoplasm through streptolysin O, a member of a large family of pore-forming toxins and cholesterol-dependent cytolysins
-
additional information
-
enzyme is incorporated into human host keratinocyte cytoplasm and membranes by aid of streptolysin O
-
additional information
-
enzyme is incorporated into human host keratinocyte cytoplasm and membranes by aid of streptolysin O
-
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Bos taurus;
Homo sapiens;
P0DF97
Streptococcus pyogenes serotype M3 (strain SSI-1);
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24000
26200
29000
31000
36300
36500
48600
-
x * 48600, recombinant C-terminally HA-tagged and His6-tagged enzyme variant SPNJ4 from Escherichia coli strain TOP10, SDS-PAGE
49000
50000
55000
100000
125000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
?
-
x * 48600, recombinant C-terminally HA-tagged and His6-tagged enzyme variant SPNJ4 from Escherichia coli strain TOP10, SDS-PAGE
?
-
x * 48600, recombinant C-terminally HA-tagged and His6-tagged enzyme variant SPNJ4 from Escherichia coli strain TOP10, SDS-PAGE
-
dimer
-
CD38 is expressed as noncovalently associated homodimer on the surface of murine B lymphocytes
additional information
-
among all identified NADases, only AA-NADase contains Cu2+ and has six disulfide-bond linkages between two peptide chains, and it has 15 free cysteine residues
additional information
-
upon stimulation with interleukin IL-8, CD38 associates with nonmuscle myosin heavy chain IIA. Association is dependent on protein kinase G-mediated phosphorylation of nonmuscle myosin heavy chain IIA and occurs through tyrosine kinase Lck
additional information
-
enzyme contains an amino-terminal domain that is not required for enzymatic activity, but involved in its translocation
additional information
-
the enzyme has multiple domains, including an N-terminal domain required for translocation and a C-terminal enzymatic domain
additional information
-
the enzyme has multiple domains, including an N-terminal domain required for translocation and a C-terminal enzymatic domain
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
-
NADase is synthesized as precursor with feeble activity. Activation by removing the carboxyl terminal region during or after secretion into culture medium
side-chain modification
side-chain modification
-
the enzyme is a glycosylphosphatidylinositol-anchored cell surface protein
side-chain modification
-
the enzyme is a glycosylphosphatidylinositol-anchored cell surface protein
-
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant wild-type and mutant enzymes, mixing of 0.001 ml of protein sample with 0.001 ml of precipitant solution containing 0.1 M imidazole, pH 7.5, and 12-24% PEG 4000, X-ray diffraction structure determination and analysis at 1.75-2.18 A resolution
-
CD38 in complex with ribosyl-2'-fluoro-deoxy-adenosine diphosphate or arabinosyl-2'-fluoro-deoxy-adenosine diphosphate ribose, soaking crystals in a solution containing either 5.2 mM inhibitor, and 100 mM MES, pH 6.0, 15% PEG 4000, and 30% glycerol, X-ray diffraction structure determination and analysis at 1.75-2.0 A resolution
wild-type and mutant E226Q in complex with cyclic ADP-ribose at 1.5 A resolution, with cyclic GDP-ribose at 1.68 A, and with NGD+ at 2.1A. Binding of cyclic ADP-ribose or cyclic GDP-ribose induce structural changes in the dipeptide E146D147 of 2.7 A. Resiudue E226 is critical in catalysis and in positioning of cyclic ADP-ribose; wild-type and mutant E226Q in complex with NAD+, NGD+, or GDP-ribose. The reaction intermediate is stabilized by polar interactions with the catalytic residue E226 rather than by a covalent linkage
-
wild-type and mutant E226Q in complex with inhibitor N1-cyclic inosine diphosphate ribose at 1.7 and 1.176 A resolution, respectively
C-terminal glycohydrolase domain of SPN (residues 191-451) in complex with IFS, vapor diffusion method, using 20%-25% (w/v) PEG 8K and 100 mM Tris-HCl (pH 8.0), at 22°C
-
purified recombinant selenomethionine-labeled enzyme C-terminal domain (residues 193-451) in complex with the full-length inhibitor IFS, sitting drop vapor-diffusion method, mixing of 0.001 ml of protein solution with 0.001 ml of reservoir solution of 20% w/v tacsimate, pH 4.0, and 20% w/v PEG 3350, 22°C, X-ray diffraction structure determination and analysis at 1.70 A resolution, single-wavelength anomalous diffraction, modelling
Q7CFI6;
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
50
additional information
-
stable to heat, activation of enzyme through boiling
45
-
2 min, 100% inactivation, DNA associated NADase; 5 min, stable, nuclear membrane NADase
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
chromatin NADase is sensitiv to Dnase
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme 81fold from reticulocytes, by lipid extracction, affinity and hydrophobic interaction chromatography, and gel filtration
-
native enzymes partially from culture supernatant, recombinant enzymes from Escherichia coli
partially, solubilization from the membrane fraction, best with CHAPS or Triton X-100
-
recombinant C-terminally HA-tagged and His6-tagged enzyme variant SPNJ4 from Escherichia coli strain TOP10
-
recombinant His-tagged wild-type and E391Q mutant SPN from Escherichia coli
-
recombinant His-tagged wild-type and mutant enzymes from Pichia apstoris culture supernatant by nickel affinity chromatography
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain Rosetta2 (DE3) by nickel affinity chromatography and gel filtration
Q7CFI6;
Talon metal affinity column chromatography, Q-Sepharose column chromatography, and S-200 gel filtration
-
wild-type and mutant enzymes by anion exchange chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of inactive enzyme variant SPNH5 from strain HSC5 and of active variant SPNJ4, expression of C-terminally HA-tagged and His6-tagged variant SPNJ4 in Escherichia coli strain TOP10
-
co-expression of N-terminally His6-tagged enzyme with inhibitor IFS in Escherichia coli strain Rosetta2 (DE3)
Q7CFI6;
DNA and amino acid sequence determination and analysis, genomic structure, recombinant expression of FLAG-tagged wild-type and mutant enzymes in HEK293 cells
-
enzymatic domain of CD38; expression of extramembrane domain in Saccharomyces cerevisiae
-
expression of wild-type and mutant enzymes in Pichia pastoris
gene hvnA, part of a four gene operon, and monocistronic gene hvnB, DNA and amino acid sequence determination and analysis, expression in Escherichia coli DH5alpha and BW23474
gene nga, cloning n Escherichia coli strain JM109, expression of wild-type and mutant enzymes
-
genotyping, SPN has a different pattern of polymorphisms than Streptococcus pyogenes housekeeping genes. The ratio of nonsynonymous to synonymous nucleotide polymorphisms reveals different patterns of evolution for NADase-active and NADase-inactive strains. SPN amino acid sequence remains preserved despite loss of NADase activity, overview
-
recombinant expression of His-tagged wild-type and E391Q mutant SPN in Escherichia coli as stable and soluble monomer in the periplasmic space
-
recombinant expression of His-tagged wild-type and mutant enzymes in Pichia apstoris and secretion to the culture medium
the C-terminal glycohydrolase domain of SPN (residues 191-451) in complex with IFS is expressed in Escherichia coli strain DL41
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
clindamycin, CLI, induces the expression of Nga, and of the other two major toxins, streptolysin O and streptokinase, in the streptococcal toxic shock syndrome, in CLI-resistant isogenic covS mutant D2TYcovS strain, overview
-
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F174G
-
site-directed mutagenesis, the point mutation F174G can turn ADP-ribosyl cyclase from a cyclase toward an NADase, overview
Q218D
-
site-directed mutagenesis, loss of NADase activity without increase in ADP-ribosyltransferase activity
Q218E
-
site-directed mutagenesis, loss of NADase activity and increase in ADP-ribosyltransferase activity
Q218D
-
site-directed mutagenesis, loss of NADase activity without increase in ADP-ribosyltransferase activity
-
Q218E
-
site-directed mutagenesis, loss of NADase activity and increase in ADP-ribosyltransferase activity
-
E124A
site-directed mutagenesis, the mutant is not inhibited by cyanidin in contrast to the wild-type enzyme
E202A
site-directed mutagenesis, the mutant is much less inhibited by cyanidin compared to the wild-type enzyme
H103A
site-directed mutagenesis, the mutant is less inhibited by cyanidin compared to the wild-type enzyme
W165A
site-directed mutagenesis, the mutant is inhibited by cyanidin like the wild-type enzyme
D330G
-
mutation of the inactive enzyme variant SPNH5 causes only a slight increase in activity, but the mutation in SPNJ4 causes an increase in activity
DELTA41-140
-
166% of wild-type activity, loss of translocation competence
DELTA41-190
-
221% of wild-type activity, loss of translocation competence
DELTA41-240
-
3.5% of wild-type activity, loss of translocation competence
E391Q
-
a catalytically nearly inactive mutant, upon transformation, SPN is toxic to Saccharomyces cerevisiae, whereas a glycohydrolase-inactive SPN allows for viability
G330D
-
mutant strain 188NADase(G330D), a derivative of 188 in which the chromosomal nga locus harbors a point mutation coding for amino acid substitution G330D in NADase. This mutation causes an enzymatically inactive NADase, associated with inactive enzyme in clinical isolates of Streptococcus pyogenes and in a deliberately constructed mutant
K289R
-
swap at residue 289 of SPNH5 does not increase activity of the inactive enzyme variant but reduces actiivty of variant SPNJ4
K289R/D330G
-
the mutation increases SPNH5 activity to the level of about 30% activity of active enzyme variant SPNJ4, but reduces activity of variant SPNJ4
L199I/Q253H/L280V
-
swaps of the 3 N-terminal residues of the enzymatic domain of variant SPNJ4 do not affect activity
R289K/G330D/I374V
-
the mutations introduced into enzyme variant SPNJ4 result in an inactivation of the enzyme
R289K/I374V
-
swaps of the the 7th and 9th polymorphic residues of variant SPNJ4 result in less activation compared to mutation D330G alone
D330G
-
mutation of the inactive enzyme variant SPNH5 causes only a slight increase in activity, but the mutation in SPNJ4 causes an increase in activity
-
K289R
-
swap at residue 289 of SPNH5 does not increase activity of the inactive enzyme variant but reduces actiivty of variant SPNJ4
-
K289R/D330G
-
the mutation increases SPNH5 activity to the level of about 30% activity of active enzyme variant SPNJ4, but reduces activity of variant SPNJ4
-
L199I/Q253H/L280V
-
swaps of the 3 N-terminal residues of the enzymatic domain of variant SPNJ4 do not affect activity
-
R289K/I374V
-
swaps of the the 7th and 9th polymorphic residues of variant SPNJ4 result in less activation compared to mutation D330G alone
-
additional information
additional information
construction of inactive hvnA/hvnB null mutant
additional information
construction of inactive hvnA/hvnB null mutant
additional information
-
synaptosomes of enzyme knock-out mutant animals contain high ADP-ribosyl cyclase activities
additional information
-
sh-RNA-mediated enzyme knockdown in HEK293 cells using shRNA-expressing lentivirus
additional information
-
sh-RNA-mediated enzyme knockdown in HEK293 cells using shRNA-expressing lentivirus
-
additional information
-
the nga mutant of strain GT01 has lost all virulence
additional information
-
derival of isogenic mutant strains deficient in expression of streptolysin O, the enzyme or both, more rapid internalization, as compared to the wild-type strain, into human keratinocytes, and reduced cytotoxicity and apoptosis occur, highly reduced enzyme content
additional information
-
derival of isogenic mutant strains deficient in expression of streptolysin O, the enzyme or both, more rapid internalization, as compared to the wild-type strain, into human keratinocytes, and reduced cytotoxicity and apoptosis occur, highly reduced enzyme content
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
simple, fast and reliable fluorescence-based assay method to evaluate the NAD+ glycohydrolase activity of cell-permeable C3 proteins
medicine
medicine
-
tumor necrosis factor alpha upregulates CD38. Induced CD38 expression enhances inflammatory gene expression by decreasing ERK1/2 phosphorylation and increasing NF kappaB activation. It negatively affects the expression of osteoclast markers. CD38 may reduce osteoclastogenesis and increase inflammatory gene induction by decreasing cellular histone deacetylase activity
medicine
-
CD157-deficient neutrophils from patients with paroxysmal nocturnal hemoglobinuria are characterized by a severely impaired diapedesis
medicine
-
treatment of lymphokine-activated killer cells with interleukin IL-8 results in internalization of CD38, which co-localizes with nonmuscle myosin heavy chain IIA and tyrosine kinase Lck. Blebbistatin blocks the internalization
medicine
-
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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