View source for 4oyw


==Crystal Structure of Human Soluble Adenylate Cyclase==
<StructureSection load='4oyw' size='340' side='right'caption='[[4oyw]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4oyw]] 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=4OYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OYW 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]] 1.7&#8491;</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4oyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oyw OCA], [https://pdbe.org/4oyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oyw RCSB], [https://www.ebi.ac.uk/pdbsum/4oyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oyw ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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;">
== 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<ref>PMID:24616449</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4oyw" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Vinkovic M]]