View source for 4usw


==Crystal structure of human soluble Adenylyl Cyclase with ATP==
<StructureSection load='4usw' size='340' side='right'caption='[[4usw]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4usw]] 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=4USW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4USW 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4usw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4usw OCA], [https://pdbe.org/4usw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4usw RCSB], [https://www.ebi.ac.uk/pdbsum/4usw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4usw 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 ==
The ubiquitous second messenger cAMP regulates a wide array of functions, from bacterial transcription to mammalian memory. It is synthesized by six evolutionarily distinct adenylyl cyclase (AC) families. In mammals, there are two AC types: nine transmembrane ACs (tmACs) and one soluble AC (sAC). Both AC types belong to the widespread cyclase class III, which has members in numerous organisms from archaeons to mammals. Class III also contains all known guanylyl cyclases (GCs), which synthesize the cAMP-related messenger cGMP in many eukaryotes and possibly some prokaryotes. Among mammalian ACs, sAC is uniquely regulated by bicarbonate, and has been proposed to be more closely related to a bacterial AC subfamily than to mammalian ACs, on the basis of sequence comparisons. Here, we used crystal structures of human sAC catalytic domains to analyze its relationships with other class III ACs and GCs, and to study its substrate selection mechanisms. Structural comparisons revealed a similarity within an sAC-like subfamily but no family-specific structure elements, and an unexpected sAC similarity to eukaryotic GCs and a potential bacterial GC. We further solved novel crystal structures of sAC catalytic domains in complex with a substrate analog, unprocessed ATP substrate, and product after soaking with ATP or GTP. The structures show a novel ATP-binding conformation, and suggest mechanisms for substrate association and recognition. Our results could explain the limited substrate specificity of sAC, suggest how specificity is increased in other cyclases, and indicate evolutionary relationships among class III enzymes, with sAC being close to a putative 'ancestor' cyclase. DATABASE: Coordinates and structure factors for the novel sAC-cat structures described have been deposited with the Worldwide PDB (www.pdb.org): ApCpp soak (entry 4usu), ATP + Ca2+ soak (entry 4usv), GTP + Mg2+ soak (entry 4ust), ATP soak (entry 4usw).

Structural analysis of human soluble adenylyl cyclase and crystal structures of its nucleotide complexes - implications for cyclase catalysis and evolution.,Kleinboelting S, van den Heuvel J, Steegborn C FEBS J. 2014 Jul 7. doi: 10.1111/febs.12913. PMID:25040695<ref>PMID:25040695</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4usw" 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: Kleinboelting S]]
[[Category: Steegborn C]]