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[[Image:1r15.gif|left|200px]]
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{{STRUCTURE_1r15|  PDB=1r15  |  SCENE=  }}
'''Aplysia ADP ribosyl cyclase with bound nicotinamide and R5P'''


==Aplysia ADP ribosyl cyclase with bound nicotinamide and R5P==
<StructureSection load='1r15' size='340' side='right'caption='[[1r15]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1r15]] 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=1R15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R15 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene></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=1r15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r15 OCA], [https://pdbe.org/1r15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r15 RCSB], [https://www.ebi.ac.uk/pdbsum/1r15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r15 ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/1r15_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r15 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==Overview==
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<ref>PMID:15016363</ref>
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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1R15 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R15 OCA].
</div>
<div class="pdbe-citations 1r15" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/15016363 15016363]
*[[Cluster of Differentiation CD38|Cluster of Differentiation CD38]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aplysia californica]]
[[Category: Aplysia californica]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Graeff, R.]]
[[Category: Graeff R]]
[[Category: Hao, Q.]]
[[Category: Hao Q]]
[[Category: Kriksunov, I A.]]
[[Category: Kriksunov IA]]
[[Category: Lee, H C.]]
[[Category: Lee HC]]
[[Category: Love, M L.]]
[[Category: Love ML]]
[[Category: Munshi, C.]]
[[Category: Munshi C]]
[[Category: Szebenyi, D M.E.]]
[[Category: Szebenyi DME]]
[[Category: Thiel, D J.]]
[[Category: Thiel DJ]]
[[Category: Adp-ribosyl cyclase]]
[[Category: Ca2+ signalling]]
[[Category: Cyclic adp-ribose]]
[[Category: Naadp]]
[[Category: X-ray crystallography]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 06:56:57 2008''