4.6.1.2: guanylate cyclase

This is an abbreviated version!
For detailed information about guanylate cyclase, go to the full flat file.

Word Map on EC 4.6.1.2

Reaction

GTP
=
3',5'-cyclic GMP
+
diphosphate

Synonyms

More, guanylyl cyclase, guanyl cyclase, STA, PGC, ANPRA, ANPRB, Atrial natriuretic peptide A-type receptor, Atrial natriuretic peptide B-type receptor, Guanylate cyclase, Guanylate cyclase 2D, retinal, Guanylate cyclase 2E, Guanylate cyclase 2F, retinal, Guanylate cyclase, olfactory, hSTAR, Intestinal guanylate cyclase, KSGC, Rod outer segment membrane guanylate cyclase, ROS-GC, ROS-GC2, STA receptor, soluble guanylyl cyclase, sGC, guanylyl cyclase C receptor, GCC, CNP-sensitive guanyly cyclase, membrane bound guanylyl cyclase, GC-B, guanylyl cyclase A, GCA, membrane bound guanylate cyclase, ROS-GC1, soluble guanylate cyclase, nitric oxid sensitive guanylyl cyclase, membrane-bound guanylate cyclase, membrane-bound GC, ratGC, NO receptor, ONE-GC, ONE-GC membrane guanylate cyclase, GC-D, mGc, membrane-bound guanylyl cyclase, NPR-B, NP-GC, CNP-sensitive guanylyl cyclase, NO-sGC, nitric-oxide-sensitive guanylyl cyclase, L1 H-NOX, L2 H-NOX, H-NOX, sGCbeta1, guanylate cyclase 1, guanylate cyclase 2, GC1, GC2, guanylyl cyclase-G, GC-G, receptor-type guanylyl cyclase, gcy-8, gcy-18, gcy-23, particulate guanylate cyclase, GC-A, guanylyl cyclase C, SONO, Gyc-88E, Gyc-89Da, Gyc-89Db, Gyca-99B, Gycb-100B, GCY-35, Tar4 protein, BR1-GC, brassinosteroid receptor 1, particulate guanylyl cyclase, soluble GC, particulate GC, nitric oxide-sensitive guanylate cyclase, NO-sensitive GC, natriuretic peptide-activated guanylate cyclase, NPR-A, guanylyl cyclase-D, guanylyl cyclase-C, GC-C, peptide hormone receptor guanylyl cyclase-C, receptor guanylyl cyclase, CsGC-YO1, membrane guanylyl cyclase receptor, guanylyl cyclase-A receptor, GC-A receptor, soluble guanylyl cyclases, NO-independent, heme-dependent soluble guanylate cyclase, NO receptor soluble guanylyl cyclase, NO-GC1, NO-GC2, rod outer segment membrane guanylate cyclase type 1, guanylate cyclase C, nitric oxide sensitive-guanylyl cyclase, sGC alpha2 inhibitory isoform, sGC alpha2 isoform, NO- and haem-independent soluble guanylate cyclase, NO- and haem-independent sGC, GTP-pyrophosphate lyase, rGC, NO-sensitive guanylyl cyclase, soluble guanylate cyclase alpha1, soluble guanylate cyclase alpha2, retGC, retinal guanylate cyclase, RET-GC1, retinal membrane guanylyl cyclase, retinal guanylyl cyclase, RetGC1, photoreceptor guanylyl cyclase, alpha1 soluble guanylyl cyclase, alpha1 sGC, NO-GC, guanylyl cyclase-A, atrial natriuretic factor receptor guanylate cyclase, ANF-RGC, membrane guanylate cyclase, sGCalpha2beta1, sGCalpha1, alpha1beta1 guanylyl cyclase, sGCbeta3, alpha1beta1 sGC, PepR1-GC, nitric oxide sensitive guanylyl cyclase, NOsGC, NO sensitive guanylyl cyclase, RetGC2, guanylate cyclase A, guanylate cyclase B, NOGC1, guanylyl cyclase B, PSK receptor, PSKR1, phytosulfokine receptor, GTP-pyrophosphate liase cyclizing, guanyl cyclase B, rhodopsin-guanylyl cyclase, CaRhGC, BERhGC, NPR A, NPR1, Pac3, Pac2, NPR2, atrial natriuretic peptide receptor 2

ECTree

     4 Lyases
         4.6 Phosphorus-oxygen lyases
             4.6.1 Phosphorus-oxygen lyases (only sub-subclass identified to date)
                4.6.1.2 guanylate cyclase

Inhibitors

Inhibitors on EC 4.6.1.2 - guanylate cyclase

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INHIBITOR
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
-
-
guanosine tetrakisphosphate
-
-
guanosine-5'-tetraphosphate
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
guanylyl cyclase activating protein 1
-
GCAP1, a Ca2+/Mg2+-binding protein, metal binding in EF-hand 4 has no role in the primary attachment of GCAP1 to the cyclase, it only triggers the activator-to-inhibitor functional switch in GCAP1, differential binding of GCAP1 mutants, e.g. E75Q/E111Q/E155Q or D100N/D102G mutants, to RetGC1 in HEK-293 cells, overview
-
H2O2
-
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
HS-142-1
-
natriuretic peptide released from the heart with acute heart failure target particulate GC, results in a decrease in UNaV and cGMP excretion together with a reduction in glomerular filtration rate and an increase in distal fractional tubular sodium reabsorption
Imidazole-HCl
-
-
ITPgammaS
-
-
lauryldimethyl N-oxide
-
-
light
-
-
-
LY 83583
LY-83583
-
inhibits the enzyme and completely blocks at 5 mM high frequency stimuli at 20 Hz/20 s-induced gLTP in superior cervical ganglia isolated from control rats
LY83583
-
a selective sGC inhibitor
lysophosphatidic acid
-
preincubations for 30 min before assessments of atrial natriuretic peptide-induced cGMP generation reveals inhibitory effects, exerted in a dose-dependent manner, elicits GC-A desensitization, protein kinase A does not block lysophosphatidic acid-induced heterologous desensitization. MEK inhibitor PD 98059 does not protect against the lysophosphatidic acid-mediated decrease in GC-A hormone sensitivity
methylene blue
metrizamide
-
-
Mg2+ATPgammaS
-
inhibits cyclase activity through a mixed, non-competitive mechanism, only observable under NO stimulation and not under basal conditions
Mg2+GTPgammaS
-
inhibits cyclase activity through a mixed, non-competitive mechanism, only observable under NO stimulation and not under basal conditions
N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine
-
-
N-methylanthraniloyl-adenosine 5'-[beta,gamma-imido]triphosphate
-
-
N-methylanthraniloyl-ADP
-
-
N-methylanthraniloyl-ATP
-
-
N-methylanthraniloyl-GDP
-
-
N-methylanthraniloyl-GTP
-
-
N-methylanthraniloyl-GTPgammaS
-
-
N-methylanthraniloyl-guanosine 5'-[beta,gamma-imido]triphosphate
-
-
N-methylanthraniloyl-ITPgammaS
-
-
N-methylanthraniloyl-xanthosine 5'-[beta,gamma-imido]triphosphate
-
-
N-methylanthraniloyl-XDP
-
-
NaCl
-
80% inhibition at 0.2 mM, affects C-type NP 1-53 stimulation of the enzyme
nitric oxide
-
-
NS-2028
O2
-
forms stable complexes with Gyc-88E(1-597), inhibits 3.2fold
octylamine
-
-
ONE-GC 880MGTTVEPEYFDQVTIYFSDIVG901
-
causes ca. 90% inhibition
ONE-GC 900VGFTTISALSEPIEVVGFLNDL921
-
most effective inhibitor, causes ca. 95% inhibition
oxaloacetate
Pb2+
-
-
phosphodiesterase inhibitor dipyridamole
-
-
-
phosphoenolpyruvate
polylysine
-
-
potassium thiocyanate
-
-
protein phosphatase from spermatozoa
-
-
-
S-nitrosocysteine
-
inhibition of sGC activity by S-nitrosocysteine occurs only in parallel with the loss of cellular glutathione suggesting that loss of sGC activity may occur as a result of the severe depletion of the reduced thiol pool that occurs after exposure of cells to S-nitrosocysteine
SDS
-
-
sGC alpha1 splice variant
inhibits the enzyme, no co-precipitation of the N1-alpha1 sGC with the beta-subunit
-
Sodium azide
-
-
sodium lauryl sarcosinate
-
-
superoxide
tetanus toxin
expression of tetanus toxin in the neurons, that express isozyme Gyc-89Da, blocks their synaptic activity; expression of tetanus toxin in the neurons, that express isozyme Gyc-89Db, blocks their synaptic activity
-
thrombospondin-1
-
thrombospondin-1 is a universal inhibitor of sGC, blocking both hemedependent and heme-independent activation
-
Trifluoperazine
-
-
UTPgammaS
-
-
XDP
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
XTP
-
basal activity of wild-type enzyme is considerably less sensitive than NO-stimulated wild-type activity
zinc (II) protophorphyrin IX
-
at higher concentrations, 2.5 µM
[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one
[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
-
-
additional information
-