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Literature summary for 3.2.2.5 extracted from

  • Liu, Q.; Graeff, R.; Kriksunov, I.A.; Jiang, H.; Zhang, B.; Oppenheimer, N.; Lin, H.; Potter, B.V.; Lee, H.C.; Hao, Q.
    Structural basis for enzymatic evolution from a dedicated ADP-ribosyl cyclase to a multifunctional NAD hydrolase (2009), J. Biol. Chem., 284, 27637-27645.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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 (Commentary)

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

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

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Aplysia californica
-
-
-
Homo sapiens P28907
-
-

Purification (Commentary)

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

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 and Products (Substrate)

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

Synonyms Comment Organism
ADPRC
-
Aplysia californica
CD38
-
Homo sapiens
NAD hydrolase
-
Homo sapiens
NADase
-
Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Aplysia californica

General Information

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