5iv3
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human soluble adenylyl cyclase in complex with alpha,beta-methyleneadenosine-5'-triphosphate and the allosteric inhibitor LRE1== | |
| + | <StructureSection load='5iv3' size='340' side='right' caption='[[5iv3]], [[Resolution|resolution]] 1.86Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5iv3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IV3 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LRI:6-chloro-N~4~-cyclopropyl-N~4~-[(thiophen-2-yl)methyl]pyrimidine-2,4-diamine'>LRI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></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=5iv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iv3 OCA], [http://pdbe.org/5iv3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iv3 RCSB], [http://www.ebi.ac.uk/pdbsum/5iv3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iv3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The prototypical second messenger cAMP regulates a wide variety of physiological processes. It can simultaneously mediate diverse functions by acting locally in independently regulated microdomains. In mammalian cells, two types of adenylyl cyclase generate cAMP: G-protein-regulated transmembrane adenylyl cyclases and bicarbonate-, calcium- and ATP-regulated soluble adenylyl cyclase (sAC). Because each type of cyclase regulates distinct microdomains, methods to distinguish between them are needed to understand cAMP signaling. We developed a mass-spectrometry-based adenylyl cyclase assay, which we used to identify a new sAC-specific inhibitor, LRE1. LRE1 bound to the bicarbonate activator binding site and inhibited sAC via a unique allosteric mechanism. LRE1 prevented sAC-dependent processes in cellular and physiological systems, and it will facilitate exploration of the therapeutic potential of sAC inhibition. | ||
| - | + | Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.,Ramos-Espiritu L, Kleinboelting S, Navarrete FA, Alvau A, Visconti PE, Valsecchi F, Starkov A, Manfredi G, Buck H, Adura C, Zippin JH, van den Heuvel J, Glickman JF, Steegborn C, Levin LR, Buck J Nat Chem Biol. 2016 Aug 22. doi: 10.1038/nchembio.2151. PMID:27547922<ref>PMID:27547922</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5iv3" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Adenylate cyclase]] | ||
[[Category: Kleinboelting, S]] | [[Category: Kleinboelting, S]] | ||
| + | [[Category: Steegborn, C]] | ||
| + | [[Category: Allosteric inhibitor lre1]] | ||
| + | [[Category: Beta-methyleneadenosine-5'-triphosphate]] | ||
| + | [[Category: Human soluble adenylyl cyclase hsac complex alpha]] | ||
| + | [[Category: Lyase]] | ||
Revision as of 05:09, 9 September 2016
Crystal structure of human soluble adenylyl cyclase in complex with alpha,beta-methyleneadenosine-5'-triphosphate and the allosteric inhibitor LRE1
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