1r12

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(New page: 200px<br /><applet load="1r12" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r12, resolution 1.7&Aring;" /> '''Native Aplysia ADP ri...)
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[[Image:1r12.jpg|left|200px]]<br /><applet load="1r12" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1r12, resolution 1.7&Aring;" />
 
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'''Native Aplysia ADP ribosyl cyclase'''<br />
 
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==Overview==
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==Native Aplysia ADP ribosyl cyclase==
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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.
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<StructureSection load='1r12' size='340' side='right'caption='[[1r12]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1r12]] is a 2 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=1R12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R12 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r12 OCA], [https://pdbe.org/1r12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r12 RCSB], [https://www.ebi.ac.uk/pdbsum/1r12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r12 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/1r12_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1r12 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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1R12 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R12 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15016363 15016363]
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</div>
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[[Category: Aplysia californica]]
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<div class="pdbe-citations 1r12" style="background-color:#fffaf0;"></div>
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[[Category: NAD(+) nucleosidase]]
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[[Category: Single protein]]
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[[Category: Graeff, R.]]
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[[Category: Hao, Q.]]
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[[Category: Kriksunov, I.A.]]
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[[Category: Lee, H.C.]]
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[[Category: Love, M.L.]]
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[[Category: Munshi, C.]]
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[[Category: Szebenyi, D.M.E.]]
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[[Category: Thiel, D.J.]]
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[[Category: adp-ribosyl cyclase]]
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[[Category: ca2+ signalling]]
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[[Category: cyclic adp-ribose]]
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[[Category: naadp]]
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[[Category: x-ray crystallography]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:10:57 2007''
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==See Also==
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*[[Cluster of Differentiation CD38|Cluster of Differentiation CD38]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aplysia californica]]
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[[Category: Large Structures]]
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[[Category: Graeff R]]
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[[Category: Hao Q]]
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[[Category: Kriksunov IA]]
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[[Category: Lee HC]]
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[[Category: Love ML]]
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[[Category: Munshi C]]
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[[Category: Szebenyi DME]]
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[[Category: Thiel DJ]]

Current revision

Native Aplysia ADP ribosyl cyclase

PDB ID 1r12

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