Structural highlights
1r15 is a 8 chain structure with sequence from Aplca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 1r0s, 1r12, 1r16, 1lbe, 1ism, 1isj, 1isi, 1ish, 1isg |
| Activity: | NAD(+) nucleosidase, with EC number 3.2.2.5 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[NADA_APLCA] Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for calcium mobilization from endoplasmic reticulum. Also has cADPr hydrolase activity.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ADP-ribosyl cyclase catalyzes the elimination of nicotinamide from NAD and cyclization to cADPR, a known second messenger in cellular calcium signaling pathways. We have determined to 2.0 A resolution the structure of Aplysia cyclase with ribose-5-phosphate bound covalently at C3' and with the base exchange substrate (BES), pyridylcarbinol, bound to the active site. In addition, further refinement at 2.4 A resolution of the structure of nicotinamide-bound cyclase, which was previously reported, reveals that ribose-5-phosphate is also covalently bound in this structure, and a second nicotinamide site was identified. The structures of native and mutant Glu179Ala cyclase were also solved to 1.7 and 2.0 A respectively. It is proposed that the second nicotinamide site serves to promote cyclization by clearing the active site of the nicotinamide byproduct. Moreover, a ribosylation mechanism can be proposed in which the cyclization reaction proceeds through a covalently bound intermediate.
ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate.,Love ML, Szebenyi DM, Kriksunov IA, Thiel DJ, Munshi C, Graeff R, Lee HC, Hao Q Structure. 2004 Mar;12(3):477-86. PMID:15016363[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chini EN, Chini CC, Kato I, Takasawa S, Okamoto H. CD38 is the major enzyme responsible for synthesis of nicotinic acid-adenine dinucleotide phosphate in mammalian tissues. Biochem J. 2002 Feb 15;362(Pt 1):125-30. PMID:11829748
- ↑ Love ML, Szebenyi DM, Kriksunov IA, Thiel DJ, Munshi C, Graeff R, Lee HC, Hao Q. ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate. Structure. 2004 Mar;12(3):477-86. PMID:15016363 doi:http://dx.doi.org/10.1016/j.str.2004.02.006
