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| <StructureSection load='3zwp' size='340' side='right'caption='[[3zwp]], [[Resolution|resolution]] 2.11Å' scene=''> | | <StructureSection load='3zwp' size='340' side='right'caption='[[3zwp]], [[Resolution|resolution]] 2.11Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3zwp]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZWP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZWP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zwp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZWP FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVU:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+[(2R,3R,4R)-4-FLUORO-3-HYDROXYTETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>AVU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1r0s|1r0s]], [[1lbe|1lbe]], [[1r16|1r16]], [[1r15|1r15]], [[1r12|1r12]], [[3zwm|3zwm]], [[3zwn|3zwn]], [[3zwo|3zwo]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AVU:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+[(2R,3R,4R)-4-FLUORO-3-HYDROXYTETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>AVU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zwp OCA], [https://pdbe.org/3zwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zwp RCSB], [https://www.ebi.ac.uk/pdbsum/3zwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zwp ProSAT]</span></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zwp OCA], [http://pdbe.org/3zwp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zwp RCSB], [http://www.ebi.ac.uk/pdbsum/3zwp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zwp ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/NADA_APLCA 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.<ref>PMID:11829748</ref> | + | [https://www.uniprot.org/uniprot/NADA_APLCA 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.<ref>PMID:11829748</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Aplca]] | + | [[Category: Aplysia californica]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Graeff, R]] | + | [[Category: Graeff R]] |
- | [[Category: Hao, Q]] | + | [[Category: Hao Q]] |
- | [[Category: Kotaka, M]] | + | [[Category: Kotaka M]] |
- | [[Category: Lee, H C]] | + | [[Category: Lee HC]] |
- | [[Category: Zhang, L H]] | + | [[Category: Zhang LH]] |
- | [[Category: Aplysia]]
| + | |
- | [[Category: Binding site]]
| + | |
- | [[Category: Cd38]]
| + | |
- | [[Category: Dp-ribosyl cyclase]]
| + | |
- | [[Category: Hydrolase]]
| + | |
- | [[Category: Hydrolysis]]
| + | |
- | [[Category: Nad]]
| + | |
- | [[Category: Protein conformation]]
| + | |
- | [[Category: Substrate specificity]]
| + | |
| Structural highlights
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]
Publication Abstract from PubMed
Cyclic ADP-ribose (cADPR) is a calcium messenger that can mobilize intracellular Ca(2+) stores and activate Ca(2+) influx to regulate a wide range of physiological processes. Aplysia cyclase is the first member of the ADP-ribosyl cyclases identified to catalyze the cyclization of NAD(+) into cADPR. The catalysis involves a two-step reaction, the elimination of the nicotinamide ring and the cyclization of the intermediate resulting in the covalent attachment of the purine ring to the terminal ribose. Aplysia cyclase exhibits a high degree of leniency towards the purine base of its substrate, and the cyclization reaction takes place at either the N1- or the N7-position of the purine ring. To decipher the mechanism of cyclization in Aplysia cyclase, we used a crystallization setup with multiple Aplysia cyclase molecules present in the asymmetric unit. With the use of natural substrates and analogs, not only were we able to capture multiple snapshots during enzyme catalysis resulting in either N1 or N7 linkage of the purine ring to the terminal ribose, we were also able to observe, for the first time, the cyclized products of both N1 and N7 cyclization bound in the active site of Aplysia cyclase.
Structural Studies of Intermediates along the Cyclization Pathway of Aplysia ADP-Ribosyl Cyclase.,Kotaka M, Graeff R, Chen Z, Zhang LH, Lee HC, Hao Q J Mol Biol. 2011 Nov 18. PMID:22138343[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
- ↑ Kotaka M, Graeff R, Chen Z, Zhang LH, Lee HC, Hao Q. Structural Studies of Intermediates along the Cyclization Pathway of Aplysia ADP-Ribosyl Cyclase. J Mol Biol. 2011 Nov 18. PMID:22138343 doi:10.1016/j.jmb.2011.11.022
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