2gvd

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[[Image:2gvd.png|left|200px]]
 
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{{STRUCTURE_2gvd| PDB=2gvd | SCENE= }}
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==Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With TNP-ATP and Mn==
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<StructureSection load='2gvd' size='340' side='right'caption='[[2gvd]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gvd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GVD 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]] 2.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=128:SPIRO(2,4,6-TRINITROBENZENE[1,2A]-2O,3O-METHYLENE-ADENINE-TRIPHOSPHATE'>128</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FKP:METHYLPIPERAZINOFORSKOLIN'>FKP</scene>, <scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=2gvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvd OCA], [https://pdbe.org/2gvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gvd RCSB], [https://www.ebi.ac.uk/pdbsum/2gvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gvd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ADCY5_CANLF ADCY5_CANLF] Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:1618857, PubMed:16766715, PubMed:19243146, PubMed:8119955, PubMed:8428899, PubMed:9748257). Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion (By similarity).[UniProtKB:O95622]<ref>PMID:10427002</ref> <ref>PMID:11087399</ref> <ref>PMID:15591060</ref> <ref>PMID:1618857</ref> <ref>PMID:16766715</ref> <ref>PMID:19243146</ref> <ref>PMID:8119955</ref> <ref>PMID:8428899</ref> <ref>PMID:9748257</ref> Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase.<ref>PMID:8428899</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/gv/2gvd_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=2gvd 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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Membrane adenylyl cyclases (mACs) play an important role in signal transduction and are therefore potential drug targets. Earlier, we identified 2',3'-O-(N-methylanthraniloyl) (MANT)-substituted purine nucleotides as a novel class of highly potent competitive mAC inhibitors (Ki values in the 10 nM range). MANT nucleotides discriminate among various mAC isoforms through differential interactions with a binding pocket localized at the interface between the C1 and C2 domains of mAC. In this study, we examine the structure/activity relationships for 2',3'-substituted nucleotides and compare the crystal structures of mAC catalytic domains (VC1:IIC2) bound to MANT-GTP, MANT-ATP, and 2',3'-(2,4,6-trinitrophenyl) (TNP)-ATP. TNP-substituted purine and pyrimidine nucleotides inhibited VC1:IIC2 with moderately high potency (Ki values in the 100 nM range). Elongation of the linker between the ribosyl group and the MANT group and substitution of N-adenine atoms with MANT reduces inhibitory potency. Crystal structures show that MANT-GTP, MANT-ATP, and TNP-ATP reside in the same binding pocket in the VC1:IIC2 protein complex, but there are substantial differences in interactions of base, fluorophore, and polyphosphate chain of the inhibitors with mAC. Fluorescence emission and resonance transfer spectra also reflect differences in the interaction between MANT-ATP and VC1:IIC2 relative to MANT-GTP. Our data are indicative of a three-site mAC pharmacophore; the 2',3'-O-ribosyl substituent and the polyphosphate chain have the largest impact on inhibitor affinity and the nucleotide base has the least. The mAC binding site exhibits broad specificity, accommodating various bases and fluorescent groups at the 2',3'-O-ribosyl position. These data should greatly facilitate the rational design of potent, isoform-selective mAC inhibitors.
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===Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With TNP-ATP and Mn===
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Broad specificity of mammalian adenylyl cyclase for interaction with 2',3'-substituted purine- and pyrimidine nucleotide inhibitors.,Mou TC, Gille A, Suryanarayana S, Richter M, Seifert R, Sprang SR Mol Pharmacol. 2006 Sep;70(3):878-86. Epub 2006 Jun 9. PMID:16766715<ref>PMID:16766715</ref>
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{{ABSTRACT_PUBMED_16766715}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2gvd" style="background-color:#fffaf0;"></div>
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[[2gvd]] is a 3 chain structure of [[Adenylyl cyclase]] with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVD OCA].
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==See Also==
==See Also==
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*[[Adenylyl cyclase|Adenylyl cyclase]]
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*[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:016766715</ref><references group="xtra"/>
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__TOC__
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[[Category: Adenylate cyclase]]
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Canis lupus familiaris]]
[[Category: Canis lupus familiaris]]
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Mou, T C.]]
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[[Category: Mou T-C]]
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[[Category: Sprang, S R.]]
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[[Category: Sprang SR]]
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[[Category: Adenylyl cyclase]]
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[[Category: Gsa]]
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[[Category: Lyase]]
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[[Category: Tnp-atp]]
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Current revision

Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With TNP-ATP and Mn

PDB ID 2gvd

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