| Structural highlights
4oym is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | NonStd Res: | , |
| Related: | 4oya, 4oyb, 4oyi, 4oyo, 4oyp, 4oyw, 4oyx, 4oyz, 4oz2, 4oz3 |
| Gene: | ADCY10, SAC (HUMAN) |
| Activity: | Adenylate cyclase, with EC number 4.6.1.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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.
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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