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2gvd

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Revision as of 15:55, 16 November 2017

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

Structural highlights

2gvd is a 3 chain structure with sequence from Bovin, Buffalo rat and Canlf. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1tl7, 1u0h
Gene:	ADCY5 (CANLF), Adcy2 (Buffalo rat), GNAS, GNAS1 (BOVIN)
Activity:	Adenylate cyclase, with EC number 4.6.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ADCY5_CANFA] This is a membrane-bound, calcium-inhibitable adenylyl cyclase. [GNAS2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. [ADCY2_RAT] This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.

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

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mou TC, Gille A, Suryanarayana S, Richter M, Seifert R, Sprang SR. Broad specificity of mammalian adenylyl cyclase for interaction with 2',3'-substituted purine- and pyrimidine nucleotide inhibitors. Mol Pharmacol. 2006 Sep;70(3):878-86. Epub 2006 Jun 9. PMID:16766715 doi:http://dx.doi.org/10.1124/mol.106.026427

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gvd"

@@ Line 1: / Line 1: @@
 ==Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With TNP-ATP and Mn==
 <StructureSection load='2gvd' size='340' side='right' caption='[[2gvd]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2gvd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Canfa Canfa]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GVD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2gvd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Canlf Canlf]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GVD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tl7|1tl7]], [[1u0h|1u0h]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADCY5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANFA]), Adcy2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNAS, GNAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADCY5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANLF]), Adcy2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNAS, GNAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] </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=2gvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvd OCA], [http://pdbe.org/2gvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gvd RCSB], [http://www.ebi.ac.uk/pdbsum/2gvd PDBsum]</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=2gvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvd OCA], [http://pdbe.org/2gvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gvd RCSB], [http://www.ebi.ac.uk/pdbsum/2gvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gvd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 2gvd" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Adenylyl cyclase|Adenylyl cyclase]]
-*[[Guanine nucleotide-binding protein|Guanine nucleotide-binding protein]]
 == References ==
 <references/>
@@ Line 41: / Line 38: @@
 [[Category: Bovin]]
 [[Category: Buffalo rat]]
-[[Category: Canfa]]
+[[Category: Canlf]]
 [[Category: Mou, T C]]
 [[Category: Sprang, S R]]

2gvd

From Proteopedia

Revision as of 15:55, 16 November 2017

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

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