1tl7: Difference between revisions
New page: left|200px<br /><applet load="1tl7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tl7, resolution 2.80Å" /> '''Complex Of Gs- With ... |
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== | ==Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate and Mn== | ||
Membrane-bound mammalian adenylyl cyclase (mAC) catalyzes the synthesis of | <StructureSection load='1tl7' size='340' side='right'caption='[[1tl7]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1tl7]] 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=1TL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TL7 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FOK:FORSKOLIN'>FOK</scene>, <scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ONM:3-O-(N-METHYLANTHRANILOYL)-GUANOSINE-5-TRIPHOSPHATE'>ONM</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=1tl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tl7 OCA], [https://pdbe.org/1tl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tl7 RCSB], [https://www.ebi.ac.uk/pdbsum/1tl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tl7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ADCY5_CANLF ADCY5_CANLF] Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:1618857, PubMed:8428899, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). 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:8428899</ref> Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase.<ref>PMID:8428899</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/tl/1tl7_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1tl7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Membrane-bound mammalian adenylyl cyclase (mAC) catalyzes the synthesis of intracellular cyclic AMP from ATP and is activated by stimulatory G protein alpha subunits (Galpha(s)) and by forskolin (FSK). mACs are inhibited with high potency by 2 '(3')-O-(N-methylanthraniloyl) (MANT)-substituted nucleotides. In this study, the crystal structures of the complex between Galpha(s).GTPgammaS and the catalytic C1 and C2 domains from type V and type II mAC (VC1.IIC2), bound to FSK and either MANT-GTP.Mg(2+) or MANT-GTP.Mn(2+) have been determined. MANT-GTP coordinates two metal ions and occupies the same position in the catalytic site as P-site inhibitors and substrate analogs. However, the orientation of the guanine ring is reversed relative to that of the adenine ring. The MANT fluorophore resides in a hydrophobic pocket at the interface between the VC1 and IIC2 domains and prevents mAC from undergoing the "open" to "closed" domain rearrangement. The K(i) of MANT-GTP for inhibition of VC1.IIC2 is lower in the presence of mAC activators and lower in the presence of Mn(2+) compared with Mg(2+), indicating that the inhibitor binds more tightly to the catalytically most active form of the enzyme. Fluorescence resonance energy transfer-stimulated emission from the MANT fluorophore upon excitation of Trp-1020 in the MANT-binding pocket of IIC2 is also stronger in the presence of FSK. Mutational analysis of two non-conserved amino acids in the MANT-binding pocket suggests that residues outside of the binding site influence isoform selectivity toward MANT-GTP. | |||
Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate.,Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR J Biol Chem. 2005 Feb 25;280(8):7253-61. Epub 2004 Dec 9. PMID:15591060<ref>PMID:15591060</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1tl7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Canis lupus familiaris]] | [[Category: Canis lupus familiaris]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Gille | [[Category: Gille A]] | ||
[[Category: Mou | [[Category: Mou TC]] | ||
[[Category: Seifert | [[Category: Seifert RJ]] | ||
[[Category: Sprang | [[Category: Sprang SR]] | ||
