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| | ==Human solAC Complexed with AMPCPP== | | ==Human solAC Complexed with AMPCPP== |
| - | <StructureSection load='4oyx' size='340' side='right' caption='[[4oyx]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='4oyx' size='340' side='right'caption='[[4oyx]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4oyx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OYX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OYX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4oyx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OYX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.89Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oya|4oya]], [[4oyb|4oyb]], [[4oyi|4oyi]], [[4oym|4oym]], [[4oyo|4oyo]], [[4oyp|4oyp]], [[4oyw|4oyw]], [[4oyz|4oyz]], [[4oz2|4oz2]], [[4oz3|4oz3]]</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=4oyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oyx OCA], [https://pdbe.org/4oyx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oyx RCSB], [https://www.ebi.ac.uk/pdbsum/4oyx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oyx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADCY10, SAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4oyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oyx OCA], [http://pdbe.org/4oyx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oyx RCSB], [http://www.ebi.ac.uk/pdbsum/4oyx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oyx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN]] Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN] Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN]] Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation.<ref>PMID:15659711</ref> <ref>PMID:17591988</ref> | + | [https://www.uniprot.org/uniprot/ADCYA_HUMAN ADCYA_HUMAN] Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation.<ref>PMID:15659711</ref> <ref>PMID:17591988</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Adenylyl cyclase|Adenylyl cyclase]] | + | *[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenylate cyclase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Vinkovic, M]] | + | [[Category: Vinkovic M]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Protein-substrate analogue complex]]
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| Structural highlights
4oyx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.89Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ADCYA_HUMAN Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
ADCYA_HUMAN Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation.[1] [2]
Publication Abstract from PubMed
Soluble adenylate cyclases catalyse the synthesis of the second messenger cAMP through the cyclisation of ATP and are the only known enzymes to be directly activated by bicarbonate. Here, we report the first crystal structure of the human enzyme that reveals a pseudosymmetrical arrangement of two catalytic domains to produce a single competent active site and a novel discrete bicarbonate binding pocket. Crystal structures of the apo protein, the protein in complex with alpha,beta-methylene adenosine 5'-triphosphate (AMPCPP) and calcium, with the allosteric activator bicarbonate, and also with a number of inhibitors identified using fragment screening, all show a flexible active site that undergoes significant conformational changes on binding of ligands. The resulting nanomolar-potent inhibitors that were developed bind at both the substrate binding pocket and the allosteric site, and can be used as chemical probes to further elucidate the function of this protein.
Crystal Structure of Human Soluble Adenylate Cyclase Reveals a Distinct, Highly Flexible Allosteric Bicarbonate Binding Pocket.,Saalau-Bethell SM, Berdini V, Cleasby A, Congreve M, Coyle JE, Lock V, Murray CW, O'Brien MA, Rich SJ, Sambrook T, Vinkovic M, Yon JR, Jhoti H ChemMedChem. 2014 Feb 24. doi: 10.1002/cmdc.201300480. PMID:24616449[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Geng W, Wang Z, Zhang J, Reed BY, Pak CY, Moe OW. Cloning and characterization of the human soluble adenylyl cyclase. Am J Physiol Cell Physiol. 2005 Jun;288(6):C1305-16. Epub 2005 Jan 19. PMID:15659711 doi:http://dx.doi.org/10.1152/ajpcell.00584.2004
- ↑ Schmid A, Sutto Z, Nlend MC, Horvath G, Schmid N, Buck J, Levin LR, Conner GE, Fregien N, Salathe M. Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP. J Gen Physiol. 2007 Jul;130(1):99-109. PMID:17591988 doi:http://dx.doi.org/jgp.200709784
- ↑ Saalau-Bethell SM, Berdini V, Cleasby A, Congreve M, Coyle JE, Lock V, Murray CW, O'Brien MA, Rich SJ, Sambrook T, Vinkovic M, Yon JR, Jhoti H. Crystal Structure of Human Soluble Adenylate Cyclase Reveals a Distinct, Highly Flexible Allosteric Bicarbonate Binding Pocket. ChemMedChem. 2014 Feb 24. doi: 10.1002/cmdc.201300480. PMID:24616449 doi:http://dx.doi.org/10.1002/cmdc.201300480
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