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EC Tree
IUBMB Comments Also acts on dATP to form 3',5'-cyclic dAMP. Requires pyruvate. Activated by NAD+ in the presence of EC 2.4.2.31 NAD(P)+---arginine ADP-ribosyltransferase.
The taxonomic range for the selected organisms is: Arthrospira platensis The enzyme appears in selected viruses and cellular organisms
Synonyms
adenylate cyclase, adenylyl cyclase, adenyl cyclase, pituitary adenylate cyclase, edema factor, adenylylcyclase, soluble adenylyl cyclase, adenylate cyclase toxin, adcy5, aciii,
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class III adenylate cyclase
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3',5'-cyclic AMP synthetase
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Adenylate cyclase, olfactive type
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Adenylyl cyclase type 10
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ATP pyrophosphate-lyase
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Ca(2+)-inhibitable adenylyl cyclase
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Ca(2+)/calmodulin activated adenylyl cyclase
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class III adenylyl cyclase
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cyclase, adenylate
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additional information
the enzyme belongs to the class III adenylyl cyclase superfamily
adenylyl cyclase
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P-O bond cleavage
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ATP diphosphate-lyase (cyclizing; 3',5'-cyclic-AMP-forming)
Also acts on dATP to form 3',5'-cyclic dAMP. Requires pyruvate. Activated by NAD+ in the presence of EC 2.4.2.31 NAD(P)+---arginine ADP-ribosyltransferase.
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ATP
3',5'-cyclic-AMP + diphosphate
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?
ATP
3',5'-cAMP + diphosphate
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ATP
3',5'-cyclic AMP + diphosphate
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?
ATP
cAMP + diphosphate
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?
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ATP
3',5'-cyclic-AMP + diphosphate
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?
ATP
3',5'-cyclic AMP + diphosphate
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?
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Mn2+
1 mM, strong activation
Ca2+
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Mg2+
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Mg2+
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3' hydroxyl group bound to a Mg-ion complexed to RP-ATP-alphaS
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1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro-1,4,4a,4b,5,8,8a,12b-octahydro-11-sulfo-1,4:5,8-dimethanotriphenylene-10-carboxylic acid
the compound defines an AC inhibitor scaffold with high affinity for human soluble isozyme and less inhibitory effect on mammalian transmembrane isozymes
1-(bromo(1-naphthyl)methyl)naphthalene
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17beta-estra-1(10),2,4-triene-2,3,17-triol
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2,3,6,23-tetrahydroxyurs-12-en-28-oic acid
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2,3-dibromo-1-(4-(hydroxy(oxido)amino)phenyl)-3-(4-quinolinyl)-1-propanone
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3,20-dioxopregn-4-en-21-yl 4-bromobenzenesulfonate
4,5,6,7-tetrachloro-3,3-bis(6-hydroxy[1,1'-biphenyl]-3-yl)-2-benzofuran-1(3H)-one
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5'-benzyl-12'-hydroxy-2'-methyl-3',6',18-trioxoergotaman
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2-hydroxyestradiol
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IC50 of about 2 microM
catechol
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noncompetetive inhibitor
additional information
structure-based development of adenylyl cyclase inhibitors, compounds exploiting the catechol estrogen binding site can produce potent, isoform discriminating adenylyl cyclase inhibitors, inhibitory potency of compounds, overview
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3,20-dioxopregn-4-en-21-yl 4-bromobenzenesulfonate
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3,20-dioxopregn-4-en-21-yl 4-bromobenzenesulfonate
discriminates between soluble isozyme and transmembrane isozymes, and appears to simultaneously block the original binding pocket and a neighboring interaction site
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additional information
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2-4fold enhancement of adenylate cyclase activity by the histidine kinase-receiver system, histidine kinase domain autophosphorylates on His572, subsequently the phosphate is transferred to the second receiver domain Asp895, which is adjacent to the CHD domain
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bicarbonate
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bicarbonate
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stimulates 2.5fold
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0.005
1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro-1,4,4a,4b,5,8,8a,12b-octahydro-11-sulfo-1,4:5,8-dimethanotriphenylene-10-carboxylic acid
Arthrospira platensis
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0.2
1-(bromo(1-naphthyl)methyl)naphthalene
Arthrospira platensis
about
0.001
17beta-estra-1(10),2,4-triene-2,3,17-triol
Arthrospira platensis
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0.1
2,3,6,23-tetrahydroxyurs-12-en-28-oic acid
Arthrospira platensis
about
0.1
2,3-dibromo-1-(4-(hydroxy(oxido)amino)phenyl)-3-(4-quinolinyl)-1-propanone
Arthrospira platensis
about
0.015
3,20-dioxopregn-4-en-21-yl 4-bromobenzenesulfonate
Arthrospira platensis
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0.1
4,5,6,7-tetrachloro-3,3-bis(6-hydroxy[1,1'-biphenyl]-3-yl)-2-benzofuran-1(3H)-one
Arthrospira platensis
about
0.07
5'-benzyl-12'-hydroxy-2'-methyl-3',6',18-trioxoergotaman
Arthrospira platensis
about
0.002
2-hydroxyestradiol
Arthrospira platensis
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IC50 of about 2 microM
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0.00036
in the presence of 1 mM Mg2+, recombinant C-terminal CyaG domain
0.011
in the presence of 1 mM Mn2+, recombinant C-terminal CyaG domain
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gene cyaC
UniProt
brenda
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brenda
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O32393_ARTPT
1202
0
133924
TrEMBL
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crystal structure analysis
complex with 2-hydroxyestradiol and alpha/beta-methylene-ATP, 20-3 A resolution
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K533E/I603R/D605C
mutant lose adenylyl cyclase activity but obtains significant guanylyl cyclase activity
additional information
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mutation of either His572 or Asp895 greatly reduces AC activity
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recombinant C-terminal domain
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expression of the N-terminally His-tagged catalytic domain of CyaC
expression of C-terminal domain as GST-fusion protein in Escherichia coli
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Kasahara, M.; Unno, T.; Yashiro, K.; Ohmori, M.
CyaG, a novel cyanobacterial adenylyl cyclase and a possible ancestor of mammalian guanylyl cyclases
J. Biol. Chem.
276
10564-10569
2001
Arthrospira platensis (Q9EXQ2), Arthrospira platensis
brenda
Steegborn, C.; Litvin, T.N.; Hess, K.C.; Capper, A.B.; Taussig, R.; Buck, J.; Levin, L.R.; Wu, H.
A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen
J. Biol. Chem.
280
31754-31759
2005
Homo sapiens, Arthrospira platensis
brenda
Linder, J.U.
Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation
Cell. Mol. Life Sci.
63
1736-1751
2006
Bacillus anthracis, Bordetella pertussis, Saccharomyces cerevisiae, Caenorhabditis elegans, Chlamydomonas reinhardtii, Chloroflexus aurantiacus, Dictyostelium discoideum, Drosophila melanogaster, Escherichia coli, Euglena gracilis, Mus musculus, Myxococcus xanthus, Pseudomonas aeruginosa, Rattus norvegicus, Sinorhizobium meliloti, Schizosaccharomyces pombe, Arthrospira platensis, Trypanosoma brucei, Ustilago maydis, Yersinia enterocolitica, Mycobacterium tuberculosis (P9WQ35), Nostoc sp. PCC 7120 = FACHB-418 (Q7A2D9), Nostoc sp. PCC 7120 = FACHB-418 (Q8YMH0), Nostoc sp. PCC 7120 = FACHB-418 (Q8YVS0), Mycobacterium tuberculosis H37Rv (P9WQ35)
brenda
Sinha, S.C.; Sprang, S.R.
Structure, mechanism, regulation and evolution of class III nucleotidyl cyclases
Rev. Physiol. Biochem. Pharmacol.
157
105-140
2007
Aeromonas hydrophila, Bacillus anthracis, Prevotella ruminicola, Bordetella pertussis, Canis lupus familiaris, Caulobacter vibrioides, Escherichia sp., Haemophilus sp., Mycobacterium tuberculosis, Yersinia pestis, Pseudomonas sp., Pseudomonas aeruginosa, Rattus norvegicus, Rhizobium etli, Sinorhizobium meliloti, Arthrospira platensis, Trypanosoma brucei, Vibrio parahaemolyticus, Yersinia sp.
brenda
Schlicker, C.; Rauch, A.; Hess, K.C.; Kachholz, B.; Levin, L.R.; Buck, J.; Steegborn, C.
Structure-based development of novel adenylyl cyclase inhibitors
J. Med. Chem.
51
4456-4464
2008
Rattus norvegicus, Arthrospira platensis (O32393), Homo sapiens (Q96PN6), Homo sapiens
brenda
Transporter Classification Database (TCDB):
8.A.85.1.4