Cloned (Comment) | Organism |
---|---|
expression of wild-type and mutant enzymes in Pichia pastoris | Aplysia californica |
expression of wild-type and mutant enzymes in Pichia pastoris | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
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 | Homo sapiens |
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 | Aplysia californica |
Protein Variants | Comment | Organism |
---|---|---|
E179G | site-directed mutagenesis | Aplysia californica |
F174G | site-directed mutagenesis, the point mutation F174G can turn ADP-ribosyl cyclase from a cyclase toward an NADase, overview | Aplysia californica |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
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 | Homo sapiens | |
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 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Aplysia californica | 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 | ? | - |
? | |
NAD+ + H2O | Homo sapiens | - |
ADP-ribose + nicotinamide | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Aplysia californica | - |
- |
- |
Homo sapiens | P28907 | - |
- |
Purification (Comment) | Organism |
---|---|
wild-type and mutant enzymes by anion exchange chromatography | Aplysia californica |
wild-type and mutant enzymes by anion exchange chromatography | Homo sapiens |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ | reaction mechanism, and structure-function relationship, overview | Aplysia californica | |
NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ | reaction mechanism, and structure-function relationship, overview | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
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 | Aplysia californica | ? | - |
? | |
additional information | substrate binding structure of wild-type and mutant enzymes, overview | Aplysia californica | ? | - |
? | |
NAD+ + H2O | - |
Homo sapiens | ADP-ribose + nicotinamide | - |
? | |
NAD+ + H2O | substrate binding structure, overview. Catalytically important CD38 residue Thr221 disfavors the cyclizing folding of the substrate, resulting in NADase being the dominant activity | Homo sapiens | ADP-ribose + nicotinamide | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ADPRC | - |
Aplysia californica |
CD38 | - |
Homo sapiens |
NAD hydrolase | - |
Homo sapiens |
NADase | - |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Aplysia californica |
General Information | Comment | Organism |
---|---|---|
additional information | structural determinants for the functional evolution from a cyclase to a hydrolase, overview | Aplysia californica |
additional information | structural determinants for the functional evolution from a cyclase to a hydrolase, overview | Homo sapiens |
physiological function | CD38 has multiple activities, i.e. in cyclic ADP-ribose, cADPR, production and degradation, as well as NAD hydrolysis as NADase | Homo sapiens |