Information on EC 4.6.1.2 - guanylate cyclase

New: Word Map on EC 4.6.1.2
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
4.6.1.2
-
RECOMMENDED NAME
GeneOntology No.
guanylate cyclase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP = 3',5'-cyclic GMP + diphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
P-O bond cleavage
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
GTP diphosphate-lyase (cyclizing; 3',5'-cyclic-GMP-forming)
Also acts on ITP and dGTP.
CAS REGISTRY NUMBER
COMMENTARY hide
9054-75-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
tiger salamander
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
sea urchin
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene CsGC-YO1
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
soluble isozyme; gene CYG12 encoding the soluble isozyme
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
during growth, 60-80% of GC activity is attributed to sGC
-
-
Manually annotated by BRENDA team
South American opossum, female and male
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
i.e. Ipomoea nil
UniProt
Manually annotated by BRENDA team
MHOM/IN/1983/AG83
SwissProt
Manually annotated by BRENDA team
Leishmania donovani MHOM/IN/1983/AG83
MHOM/IN/1983/AG83
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J background
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
strain 51s
-
-
Manually annotated by BRENDA team
strain 51s
-
-
Manually annotated by BRENDA team
frog
-
-
Manually annotated by BRENDA team
toad
-
-
Manually annotated by BRENDA team
subsp. acutidens
-
-
Manually annotated by BRENDA team
strain B2086
-
-
Manually annotated by BRENDA team
strain B2086
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-deoxy-GTP
?
show the reaction diagram
-
effective substrate
-
-
?
2'-O-(N-methylanthraniloyl) guanosine 5'-triphosphate
?
show the reaction diagram
-
-
-
-
?
ATP
3',5'-cyclic AMP + diphosphate
show the reaction diagram
ATP
adenosine cyclic 3'-5'monophosphate + diphosphate
show the reaction diagram
-
-
-
?
CTP
3',5'-cyclic CMP + diphosphate
show the reaction diagram
-
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
show the reaction diagram
GTP
3',5'-cyclic-GMP + diphosphate
show the reaction diagram
GTPgammaS
?
show the reaction diagram
-
-
-
-
?
guanosine 5'-beta,gamma-methylene triphosphate
?
show the reaction diagram
-
-
-
-
?
guanosine-5'-[alpha,beta-methylene]triphosphate
?
show the reaction diagram
-
-
-
-
?
guanyl-(beta,gamma-methylene)-diphosphate
?
show the reaction diagram
-
-
-
?
guanyl-imidodiphosphate
?
show the reaction diagram
-
-
-
?
UTP
3',5'-cyclic UMP + diphosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GTP
3',5'-cyclic GMP + diphosphate
show the reaction diagram
GTP
3',5'-cyclic-GMP + diphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
-
activation in presence of Ca2+
tin(IV) protophorphyrin IX (2+)
-
activation
zinc (II) protophorphyrin IX
-
activation at nM concentrations
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaN3
-
activation
NaNO3
-
activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
17beta-estradiol
-
decreases enzyme activity in immature rats, while the amount of sGC alpha subuit increases, estrogen receptor-dependent effects, overview
1H-(1,2,4)-oxadiazole-(4,3-a)quinoxalin-1-one
-
-
1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one
1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1one
1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one
-
effectively blocks guanylyl cyclase activity in response to low O2 levels
1H-[1,2,4]-oxadiazole[4,3-a]quinoxalin-1-one
i.e. ODQ, a highly selective sGC inhibitor; i.e. ODQ, a highly selective sGC inhibitor
1H-[1,2,4]oxadiazolo [4,3,-a]quinoxalin-1-one
1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one
-
i.e. ODQ, a sGC inhibitor
1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one
-
i.e. ODQ
1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one
1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin 1-one
decreases infectivity of promastigotes
1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one
-
-
1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one
1H-[1,2,4]oxadiazolo[4.3a]quinoxalin-1-one
-
inhibition of the enzyme is blocked by 8-bromo-cGMP or L-arginine
2'(3')-O-BODIPY-FL-guanosine 5'-[beta,gamma-imido]triphosphate
-
-
2',3'-O-(2,4,6-trinitrophenyl)-ADP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-AMP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-ATP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-CTP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-GDP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-GTP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-UTP
-
-
2'-dADP
-
mixture of competitive and noncompetitive inhibition, binding to the substrate site excludes the substrate GTP, whereas binding to the noncompetitive site has no effect on GTP binding, although the resulting complex is catalytically inactive. It binds to the high and low affinity sites with equivalent affinities. BAY 41-2272, which shares an analogous core structure to YC-1, fully inhibits 2'-dADP binding to the low affinity site, whereas the inhibition by YC-1 is incomplete
2'-deoxy-3'-O-(N-methylanthraniloyl)-ATP
-
-
2'-deoxy-3'-O-(N-methylanthraniloyl)-GDP
-
-
2'-deoxy-3'-O-(N-methylanthraniloyl)-GTP
-
-
2'-deoxy-3'-O-(N-methylanthraniloyl)-guanosine 5'-[beta,gamma-imido]triphosphate
-
-
2'-dUTP
-
-
3',5'-cyclic GMP
-
20 mM, 20-30% competitive inhibition
4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one
6-(ethoxymethyl)-1-methyl-1,4,5,6-tetrahydropyrrolo[2,3-g]indazole
-
-
6-(ethoxymethyl)-1-phenyl-1,4,5,6-tetrahydropyrrolo[2,3-g]indazole
-
-
6-(ethoxymethyl)-5,6-dihydro-4H-[1,2]oxazolo[5,4-e]indole
-
-
6-(ethoxymethyl)-6H-[1,2]oxazolo[5,4-e]indole
-
-
6-anilino-5,8-quinolinedione
6-anilino-quinoline-5-8-quinone
decreases infectivity of promastigotes
6H-[1,2,4]oxadiazolo[4,3-d]pyrido[3,2-b][1,4]oxazin-9-one
-
-
8-(4-methoxyphenyl)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]-benzoxazin-1-one
-
-
8-aza-3ATP
-
inhibition of basal and sodium nitroprusside activated sGC activity
8-bromo-4H-[1,2,4]oxadiazolo[3,4-c]benzoxazin-1-one
-
NS 2028
8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one
-
i.e. NS-2028, a selective sGC inhibitor, 95% inhibition of enzyme activity at 0.01 mM, inhibits cell proliferation
8-Bromo-cGMP
-
-
8-oxoguanosine triphosphate
8-[3-(trifluoromethyl)phenyl]-4H-[1,2,4]oxadiazolo[3,4-c]-benzoxazin-1-one
-
-
9-chloro-12-oxo-6,12-dihydroquinazolino[2,3-c][1,4]-benzoxazine
-
-
adenosine 5'-beta,gamma-imido triphosphate
-
competitive inhibitior, reduces the Bmax for the binding of guanosine 5'-beta,gamma-methylene triphosphate, is tightly and selectively associated with the high affinity site
adenosine-5'-tetraphosphate
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
ADPbetaS
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
aldosterone
-
diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase ROS levels and induce oxidative posttranslational modification of Cys122, a beta1-subunit cysteinyl residue
atrial natriuretic peptide
-
elicits GC-A desensitization, can induce decreased GC-A activity in MA-10 Leydig cells, based on mechanisms directly affecting the hormone responsiveness of the receptor. Protein kinase A blocks homologous atrial natriuretic peptide induced desensitization, in which cGMP is generated as second messenger
-
BaY 63-2521
-
the sGC inhibitor gives apositive effect in severe pulmonary hypertention patients
benzamidine
-
-
BODIPY-FL-GTPgammaS
-
-
Ca2+ ionophore A23187
-
Ca2+-dependent inhibition of sGC can be achieved with the Ca2+ ionophore A23187 (0.01 mM)
Calmidazolium
-
uncompetitive inhibition, time-dependent inhibition at 0.03 mM, pre-treatment of sGC with calmidazolium, followed by filtration, causes an 80% inhibition of sGC activation by nitric oxide and a 23% inhibition of activation by protoporphyrin IX
CO
-
forms stable complexes with Gyc-88E(1-597), inhibits 2.9fold
CuSO4
-
-
D-myo-inositol 1,4,5-trisphosphate
-
-
dATP
-
-
diphosphate
DNIC-G
-
a dinitrosyl iron complex, solutions contain 18fold molar excess of free thiosulfate, inhibition of the NO-stimulated enzyme, inhibited by GSH
DNIC-Y
-
a dinitrosyl iron complex, no free thiosulfate in solutions of the binuclear complex DNIC-Y, inhibition of the NO-stimulated enzyme, inhibited by GSH
Fe2+
-
-
Fe3+
-
-
GDPbetaS
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
Go6976
-
competitive inhibitor. Go6976 reduces GTP binding to the catalytic site of isoforms GC-A and GC-B. Inhibition of isoform GC-B is minimal in the absence of ATP and 1 mM ATP increases the inhibition 4fold
GTPgammaS
-
inhibits mastoparan-induced activation
guanosine 5'-(beta,gamma-imido)triphosphate
-