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| | <StructureSection load='3maa' size='340' side='right'caption='[[3maa]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='3maa' size='340' side='right'caption='[[3maa]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3maa]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin], [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [https://en.wikipedia.org/wiki/Canlf Canlf]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3e8a 3e8a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MAA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3maa]] 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3e8a 3e8a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MAA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TAT:ADENOSINE-5-RP-ALPHA-THIO-TRIPHOSPHATE'>TAT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3c16|3c16]], [[3c15|3c15]], [[3c14|3c14]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TAT:ADENOSINE-5-RP-ALPHA-THIO-TRIPHOSPHATE'>TAT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADCY5, ADENYLYL CYCLASE TYPE V ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANLF]), Adcy2, ADENYLYL CYCLASE TYPE II ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNAS, GNAS1 ([https://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'>[https://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3maa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3maa OCA], [https://pdbe.org/3maa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3maa RCSB], [https://www.ebi.ac.uk/pdbsum/3maa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3maa ProSAT]</span></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=3maa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3maa OCA], [https://pdbe.org/3maa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3maa RCSB], [https://www.ebi.ac.uk/pdbsum/3maa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3maa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ADCY5_CANFA ADCY5_CANFA]] This is a membrane-bound, calcium-inhibitable adenylyl cyclase. [[https://www.uniprot.org/uniprot/GNAS2_BOVIN 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. [[https://www.uniprot.org/uniprot/ADCY2_RAT ADCY2_RAT]] This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenylate cyclase]] | + | [[Category: Bos taurus]] |
| - | [[Category: Bovin]] | + | [[Category: Canis lupus familiaris]] |
| - | [[Category: Buffalo rat]]
| + | |
| - | [[Category: Canlf]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mou, T C]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Sprang, S R]] | + | [[Category: Mou T-C]] |
| - | [[Category: Adenylyl cyclase]]
| + | [[Category: Sprang SR]] |
| - | [[Category: Atp-alpha-]]
| + | |
| - | [[Category: Calcium ion]] | + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| Structural highlights
3maa is a 3 chain structure with sequence from Bos taurus, Canis lupus familiaris and Rattus norvegicus. This structure supersedes the now removed PDB entry 3e8a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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][1] [2] [3] [4] [5] [6] [7] Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase.[8]
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
Type V and VI mammalian adenylyl cyclases (AC5, AC6) are inhibited by Ca(2+) at both sub- and supramicromolar concentration. This inhibition may provide feedback in situations where cAMP promotes opening of Ca(2+) channels, allowing fine control of cardiac contraction and rhythmicity in cardiac tissue where AC5 and AC6 predominate. Ca(2+) inhibits the soluble AC core composed of the C1 domain of AC5 (VC1) and the C2 domain of AC2 (IIC2). As observed for holo-AC5, inhibition is biphasic, showing "high-affinity" (K(i) = approximately 0.4 microM) and "low-affinity" (K(i) = approximately 100 microM) modes of inhibition. At micromolar concentration, Ca(2+) inhibition is nonexclusive with respect to pyrophosphate (PP(i)), a noncompetitive inhibitor with respect to ATP, but at >100 microM Ca(2+), inhibition appears to be exclusive with respect to PP(i). The 3.0 A resolution structure of Galphas.GTPgammaS/forskolin-activated VC1:IIC2 crystals soaked in the presence of ATPalphaS and 8 microM free Ca(2+) contains a single, loosely coordinated metal ion. ATP soaked into VC1:IIC2 crystals in the presence of 1.5 mM Ca(2+) is not cyclized, and two calcium ions are observed in the 2.9 A resolution structure of the complex. In both of the latter complexes VC1:IIC2 adopts the "open", catalytically inactive conformation characteristic of the apoenzyme, in contrast to the "closed", active conformation seen in the presence of ATP analogues and Mg(2+) or Mn(2+). Structures of the pyrophosphate (PP(i)) complex with 10 mM Mg(2+) (2.8 A) or 2 mM Ca(2+) (2.7 A) also adopt the open conformation, indicating that the closed to open transition occurs after cAMP release. In the latter complexes, Ca(2+) and Mg(2+) bind only to the high-affinity "B" metal site associated with substrate/product stabilization. Ca(2+) thus stabilizes the inactive conformation in both ATP- and PP(i)-bound states.
Structural basis for inhibition of mammalian adenylyl cyclase by calcium.,Mou TC, Masada N, Cooper DM, Sprang SR Biochemistry. 2009 Apr 21;48(15):3387-97. PMID:19243146[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tesmer JJ, Sunahara RK, Johnson RA, Gosselin G, Gilman AG, Sprang SR. Two-metal-Ion catalysis in adenylyl cyclase. Science. 1999 Jul 30;285(5428):756-60. PMID:10427002
- ↑ Tesmer JJ, Dessauer CW, Sunahara RK, Murray LD, Johnson RA, Gilman AG, Sprang SR. Molecular basis for P-site inhibition of adenylyl cyclase. Biochemistry. 2000 Nov 28;39(47):14464-71. PMID:11087399
- ↑ Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR. Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate. J Biol Chem. 2005 Feb 25;280(8):7253-61. Epub 2004 Dec 9. PMID:15591060 doi:http://dx.doi.org/10.1074/jbc.M409076200
- ↑ Ishikawa Y, Katsushika S, Chen L, Halnon NJ, Kawabe J, Homcy CJ. Isolation and characterization of a novel cardiac adenylylcyclase cDNA. J Biol Chem. 1992 Jul 5;267(19):13553-7. PMID:1618857
- ↑ 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
- ↑ Mou TC, Masada N, Cooper DM, Sprang SR. Structural basis for inhibition of mammalian adenylyl cyclase by calcium. Biochemistry. 2009 Apr 21;48(15):3387-97. PMID:19243146 doi:http://dx.doi.org/10.1021/bi802122k
- ↑ Katsushika S, Kawabe J, Homcy CJ, Ishikawa Y. In vivo generation of an adenylylcyclase isoform with a half-molecule motif. J Biol Chem. 1993 Feb 5;268(4):2273-6. PMID:8428899
- ↑ Katsushika S, Kawabe J, Homcy CJ, Ishikawa Y. In vivo generation of an adenylylcyclase isoform with a half-molecule motif. J Biol Chem. 1993 Feb 5;268(4):2273-6. PMID:8428899
- ↑ Mou TC, Masada N, Cooper DM, Sprang SR. Structural basis for inhibition of mammalian adenylyl cyclase by calcium. Biochemistry. 2009 Apr 21;48(15):3387-97. PMID:19243146 doi:http://dx.doi.org/10.1021/bi802122k
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