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CSA entry for 1r16
Original Entry
Title:
Hydrolase
Compound:
Adp-ribosyl cyclase
Mutant:
No
UniProt/Swiss-Prot:
P29241-NADA_APLCA
EC Class:
3.2.2.5
Other CSA Entries:
Overview of all sites for 1r16
Homologues of 1r16
Entries for UniProt/Swiss-Prot: P29241
Entries for EC: 3.2.2.5
Other Databases:
PDB entry: 1r16
PDBsum entry: 1r16
UniProt/Swiss-Prot: P29241
IntEnz entry: 3.2.2.5
Literature Report:
Introduction:
ADP-ribosyl cyclase catalyses the elimination of nicotinamide from NAD and cyclisation of cADPR. It has been identified in many organisms from microbes to mammals.

The product from this enzyme, cADPR, is a second messenger in cellular calcium signalling pathways and it regulates the concentration of calcium ions in a variety of mammalian and non-mammalian cell types.
Mechanism:
Glu179 nucleophilically attacks the ribose C1' which nicotinamide attached to. The nucleophilic attack eliminates the nicotinamide and leads to the formation of a Glu179-R5P intermediate. N1 of purine group then acts as a nucleophile to attack the ester bond between Glu179 and ribose, resulting in cyclisation to form cADPR. Glu98 provides stabilisation of hydrolysis at ribose C1' by Glu179.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 98 122Sidechain
ElectrostaticTransition state
Stabilise the hydrolysis reaction at ribose C1' by Glu 179
Evidence from paper Evidence concerns Evidence type
PubMed ID 15016363 Current protein Conservation of residue
PubMed ID 15016363 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 10521467 Current protein Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 179 203Sidechain
NucleophileSubstrate
A nucleophile that attacks the ribose C1' to eliminate nicotinamide and form a covalent intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15016363 Current protein Mutagenesis of residue
PubMed ID 15016363 Current protein Residue is covalently bound to intermediate, based on structural data
References:
1
ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate.
M. L. Love and D. M. Szebenyi and I. A. Kriksunov and D. J. Thiel and C. Munshi and R. Graeff and H. C. Lee and Q. Hao
Structure (Camb) 12, (3) 477-86, (2004).
15016363
2
Characterization of the active site of ADP-ribosyl cyclase.
C. Munshi and D. J. Thiel and I. I. Mathews and R. Aarhus and T. F. Walseth and H. C. Lee
J Biol Chem 274, (43) 30770-7, (1999).
10521467
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