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Mechanism
editBased on the calculation of free energy in the 13 possible methods of class III the image above is the proposed mechanism for Adenylyl cyclase form cAMP. The Mechanism is listed below[1]:ACS [1] 10.1021-acs.biochem.5b00655Figure1 (1) — Preceding unsigned comment added by Aflores66 (talk • contribs) 14:32, 6 November 2018 (UTC) The process starts with a dehydration of ATP, by which the protein is transferred to the phosphate group. Which causes two magnesium ions to make a conformation change. The change allows 3’O to be a better nucleophile and work with the phosphate. [1] The most crucial step in calculating this proposed mechanism was matching the final concert phosphorylation of the 3’ribosyl position in the final transition state of the mechanism. The calculate windowed has a precise window.
Structure
editThe general structure of mammalian adenylyl cyclase is found to consist of four main regions[2]. Two of which are transmembrane regions called M1 and M2, and the other two are cytoplasmic regions called C1 and C2. The transmembrane regions of M1 and M2 contain six helices in each. The cytoplasmic regions of C1 and C2 are divided into two subcategories of C1a, C1b, C2a, and C2b.
C1a and C2a subdomains are homologous and form an intramolecular ‘dimer’ that forms the active site. However, C1b and C2b are not similar at all. C1b is much larger than C2b and contains multiple allosteric sites. C2b is so small and is unknown in function.
The C1a and C2a subdomains are homologous and form an intramolecular 'dimer' that forms the active site.
In Mycobacterium tuberculosis, the AC-III polypeptide is only half as long, comprising one 6-transmembrane domain followed by a cytoplasmic domain, but two of these form a functional homodimer that resembles the mammalian architecture.
Function
editThe most well known function of adenylyl cyclase is its role in activating cyclic adenosine monophosphate (cAMP/cyclic AMP) in signal transduction pathways (specifically extracellular to intracellular via protein kinase A)[3]. These pathways occur via a cascade effect where a G protein is activated and it in turn activates adenylyl cyclase which catalyzes the synthesis of the secondary messenger cAMP from ATP[3]. Cyclic AMP thereby induces a cellular response.
Adenylyl cyclase has also been indicated to have a role in “memory formation...as a coincidence detector.”[4][5][6][7] “A soluble (non-membrane bound) form of adenylyl cyclase…” was also found to be characterized in mammalian sperm where it is activated by a bicarbonate ion[3]. The final two functions listed being still in need of further research as there is no more information available at this time.
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Example of a signal transduction pathway as activated by a hormone leading to a cellular response where adenylyl cyclase converts ATP to cAMP.
References
edit- ^ Hahn, David K.; Tusell, Jose R.; Sprang, Stephen R.; Chu, Xi (2015-10). "Catalytic Mechanism of Mammalian Adenylyl Cyclase: A Computational Investigation". Biochemistry. 54 (40): 6252–6262. doi:10.1021/acs.biochem.5b00655. ISSN 0006-2960. PMC 5156327. PMID 26393535.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Steegborn, Clemens (2014-12). "Structure, mechanism, and regulation of soluble adenylyl cyclases - similarities and differences to transmembrane adenylyl cyclases". Biochimica Et Biophysica Acta. 1842 (12 Pt B): 2535–2547. doi:10.1016/j.bbadis.2014.08.012. ISSN 0006-3002. PMID 25193033.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c "Adenylyl Cyclase". www.vivo.colostate.edu. Retrieved 2018-11-14.
- ^ Willoughby, Debbie; Cooper, Dermot M. F. (2007-07). "Organization and Ca2+ Regulation of Adenylyl Cyclases in cAMP Microdomains". Physiological Reviews. 87 (3): 965–1010. doi:10.1152/physrev.00049.2006. ISSN 0031-9333.
{{cite journal}}: Check date values in:|date=(help) - ^ Mons, N.; Guillou, J.-L.; Jaffard, R. (1999-04-01). "The role of Ca 2+ /calmodulin-stimulable adenylyl cyclases as molecular coincidence detectors in memory formation". Cellular and Molecular Life Sciences (CMLS). 55 (4): 525–533. doi:10.1007/s000180050311. ISSN 1420-682X.
- ^ Hanoune, Jacques; Defer, Nicole (2001-04). "REGULATION ANDROLE OFADENYLYLCYCLASEISOFORMS". Annual Review of Pharmacology and Toxicology. 41 (1): 145–174. doi:10.1146/annurev.pharmtox.41.1.145. ISSN 0362-1642.
{{cite journal}}: Check date values in:|date=(help) - ^ Neve, Kim A.; Seamans, Jeremy K.; Trantham-Davidson, Heather (2004-01). "Dopamine Receptor Signaling". Journal of Receptors and Signal Transduction. 24 (3): 165–205. doi:10.1081/rrs-200029981. ISSN 1079-9893.
{{cite journal}}: Check date values in:|date=(help)