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GTP
3',5'-cyclic GMP + diphosphate
ATP
3',5'-cyclic AMP + diphosphate
-
-
-
-
?
ATP
adenosine cyclic 3'-5'monophosphate + diphosphate
-
-
-
?
GTP
3',5'-cGMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
GTP
3',5'-cyclic-GMP + diphosphate
-
-
-
-
?
guanosine 5'-beta,gamma-methylene triphosphate
?
-
-
-
-
?
UTP
3',5'-cyclic UMP + diphosphate
-
-
-
-
?
additional information
?
-
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
cGMP is involved in transmitting the NO activating signals to a variety of downstream effectors such as cyclicnucleotide-gated channels, protein kinases, and phosphodiesterases
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
664860, 665511, 666248, 679399, 680671, 681631, 684348, 690841, 691656, 692446, 693082, 693256, 693267, 694270, 694411 -
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
ir
GTP
3',5'-cyclic GMP + diphosphate
-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
cGMP is involved in transmitting the NO activating signals to a variety of downstream effectors such as cyclicnucleotide-gated channels, protein kinases, and phosphodiesterases
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
the guanylyl cyclase messenger system is potentially responsive to hormones/neurotranmitters that may control the degree of relaxation in this vascular tissue
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
sGC activity plays an important role in a variety of aspects of the cardiovascular system, regulatory mechanisms, overview. sGC has an anti-proliferative effect on smooth muscle cells
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
sGC produces cGMP, a second messenger required for normal vascular smooth muscle cell, VSMC, relaxation. Activating NADPH oxidase in bovine aortic VSMC increases ROS levels and induces oxidative posttranslational modification of Cys122, a beta1-subunit cysteinyl residue of the guanylate cyclase leading to its inhibition
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
the enzyme is involved in regualtion of artery contaction, enzyme activation by NO leads to increased pulmonary artery relaxation
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
the retinal isozyme retGC-1 influences transducin movement, not through its cyclase activity, but through direct interaction with Galphat protein, overview
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
GTP in form of MgGTP2-
-
-
?
GTP
3',5'-cyclic GMP + diphosphate
-
GTP in form of MnGTP2-
-
-
?
GTP
?
-
-
-
-
?
additional information
?
-
-
2'-deoxy-3'-GMP and cGMP exhibit no detectable affinity for the enzyme
-
-
?
additional information
?
-
-
GMPNH-P, GMPCH-P and N-methylanthraniloyl 2'-GTP are poor substrates
-
-
?
additional information
?
-
-
heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide
-
-
?
additional information
?
-
-
sGC role in vascular system diseases and failures, overview
-
-
?
additional information
?
-
-
the enzyme binds the human rod Galphat protein without altering cyclase activity, interactions with ligands, overview
-
-
?
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1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one
-
-
2'(3')-O-BODIPY-FL-guanosine 5'-[beta,gamma-imido]triphosphate
-
-
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
-
-
4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one
-
i.e. NS-2028, acts via the heme domain
6-anilino-5,8-quinolinedione
-
-
8-oxoguanosine triphosphate
-
i.e. oxo8GTP, a potent inhibitor of nitric oxide-stimulated soluble guanylyl cyclase
adenosine 5'-beta,gamma-imido triphosphate
-
competitive inhibitor, reduces the Bmax for the binding of guanosine 5'-beta,gamma-methylene triphosphate, is tightly and selectively associated with the high affinity site
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
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
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
GTPgammaS
-
inhibits mastoparan-induced activation
guanosine tetrakisphosphate
-
-
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
lauryldimethyl N-oxide
-
-
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
phosphodiesterase inhibitor dipyridamole
-
-
-
potassium thiocyanate
-
-
sodium lauryl sarcosinate
-
-
zinc (II) protophorphyrin IX
-
at higher concentrations, 2.5 µM
[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one
-
-
ATP
-
-
ATP
-
mechanism involving ATP pre-binding is physiologically relevant to activation of retinal guanylate cyclase, inhibition at high concentrations
ATP
-
80% inhibition at 0.1 mM, affects C-type NP 1-53 stimulation of the enzyme, in the presence of Mn2+ inhibition of mastoparan-induced activation of the enzyme
ATP
-
inhibition by ATP of GC activity stimulated by NO
Ca2+
-
-
Ca2+
-
inhibition of both, the basal and NO-stimulated forms of sGC, competitive vs. Mg2+, noncompetitive vs. MgGTP
additional information
-
desensitization of the enzyme to NO and inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation through dinitrosyl iron complexes, which is slowly reversible by GSH, overview
-
additional information
-
effects of activators and inhibitors on enzyme regulation, overview
-
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3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene
stimulates via release of NO
2'-deoxy-3'-GMP
-
the addition of the effector to CO-activated enzyme causes the original 6-coordinate CO-heme to convert to an end product that is an equimolar mixture of a 5- and a new 6-coordinate CO-heme
2,2-diethyl-1-nitroso-oxyhydrazine
-
70-80% activation at 0.01 mM in presence of 2 mM GSH
3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene
stimulates via release of NO
A-350619
-
a heme-dependent stimulator of sGC, structurally not related to YC-1, but synergistic to YC-1 and sodium nitroprusside for the binding site
A-778935
-
i.e. cis-3-[2-(2,2-dimethyl-propylsulfanyl)pyridin-3-yl]-N-(3-hydroxycyclohexyl-)acrylamide, derived from the YC-1 structure, activates the enzyme is a synergistic fashion with the NO donor sodium nitroprusside
ATP
-
mechanism involving ATP pre-binding is physiologically relevant to activation of retinal guanylate cyclase, inhibition at high concentrations
atrial natriuretic peptide
-
activation of the particulate form
-
C-type natriuretic peptide
-
-
-
C-type NP 1-53
-
activation in a dose-dependent manner
-
cone-specific calcium sensor guanylate cyclase activating protein 4
-
encoded by gene zGCAP4 from zebrafish, cloning and expression in Escherichia coli, zGCAP4 is a strong activator of membrane-bound guanylate cyclases from bovine retina, mainly present as a monomer and showing half-maximal activation at 520-570 nM free Ca2+ concentration
-
Foscarnet
-
the addition of the effector to CO-activated enzyme causes the original 6-coordinate CO-heme to convert to an end product that is an equimolar mixture of a 5- and a new 6-coordinate CO-heme
G protein alpha subunit
-
-
-
GTPgammaS
-
increases activity to 58%
guanylate-activating protein
-
proteins GCAP-1 and GCAP-2, Ca2+-dependent negative feedback control
-
mastoparan
-
most powerful activator, activation in a dose-dependent manner
natriuretic peptide
-
-
-
peroxynitrite
-
activation in presence of GSH
protoporphyrin IX
-
0.001 mM activates untreated sGC with around half the effectiveness of nitric oxide
Triton X-100
-
activation
additional information
-
effects of activators and inhibitors on enzyme regulation, overview
-
BAY 41-2272
-
-
BAY 41-2272
-
allosteric activator
BAY 41-2272
-
one molecule is required for maximal enzyme activation and is tightly associated with sGC
BAY 41-2272
-
the addition of the effector to CO-activated enzyme causes the original 6-coordinate CO-heme to convert to an end product that is an equimolar mixture of a 5- and a new 6-coordinate CO-heme
CO
-
-
CO
-
ferrous soluble guanylate cyclase binds CO as two reversible steps. The primary step leads to the full conversion of the ferrous enzyme to the 6-coordinate CO-heme, followed by the slower second step leading to a partial conversion of the 6-coordinate CO-heme to the 5-coordinate CO-heme. Reaction may folow a multistep mechanism, in which the 5-coordinate CO-heme is led by CO release from a putative bis-carbonyl intermediate that is likely provided by the binding of a second CO to the 6-coordinate CO-heme
hydrogencarbonate
ED50 value of 27 mM. Stimulation is more powerful in the presence of activating protein GCAP1 or GCAP2 at low concentrations of Ca2+
hydrogencarbonate
ED50 value of 39 mM. When applied to retinal photoreceptors, hydrogencarbonate enhances the circulating current, decreases sensitivity to flashes, and accelerates flash response kinetics
NO
-
-
NO
-
perfect heme ligand, serves as an effector of enzyme activation via conformational transitions
NO
-
about 5000fold activation over basal level, mechanism for NO receptor activation and its modulation by GTP, ATP, and allosteric agents, model formation comprising a module in which NO, the nucleotides, and allosteric agents bind and the protein undergoes a conformational change, dovetailing with a catalytic module where GTP is converted to cGMP and diphosphate, enzyme-linked receptor mechanism, overview
NO
-
activates the soluble guanylyl cyclase
NO
-
activation of sGC by NO, released from 2,2-diethyl-1-nitroso-oxyhydrazine, is a link to the nitroglycerin biotransformation by mitochondrial aldehyde dehydrogenase, ALDH2
NO
-
binding of NO to a regulatory heme group at the beta-subunit of the protein results in 100fold stimulation of cGMP formation, NO is involved in the vascular NO/cGMP signalling, dysfunction of the signaling is thought to contribute to a wide variety of cardiovascular disorders
NO
-
the enzyme activation by NO leads to increased pulmonary artery relaxation, the activation is inhibited by heme depletion through heme oxygenase-1 induction
sodium nitroprusside
-
-
sodium nitroprusside
-
activation of the soluble form
sodium nitroprusside
-
synergistic to YC-1 and A-350619 for the binding site
YC-1
-
allosteric activator
YC-1
-
synergistic with NO, blocked by 1H-[1,2,4]oxidazolol[4,3a]quinoxalin-1-one
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Kaever, V.; Szamel, M.; Goppelt, M.; Resch, K.
Characterization and subcellular localization of nucleotide cyclases in calf thymus lymphocytes
Biochim. Biophys. Acta
776
133-143
1984
Bos taurus
brenda
Gorczyca, W.A.; VanHooser, J.P.; Palczewski, K.
Nucleotide inhibitors and activators of retinal guanylyl cyclase
Biochemistry
33
3217-3222
1994
Bos taurus
brenda
Gerzer, R.; Hofmann, F.; Schultz, G.
Purification of a soluble, sodium-nitroprusside-stimulated guanylate cyclase from bovine lung
Eur. J. Biochem.
116
479-486
1981
Bos taurus
brenda
Fleischman, D.; Denisevich, M.
Guanylate cyclase of isolated bovine retinal rod axonemes
Biochemistry
18
5060-5066
1979
Bos taurus
brenda
Krishnan, N.; Fletcher, R.T.; Chader, G.J.; Krishna, G.
Characterization of guanylate cyclase of rod outer segments of the bovine retina
Biochim. Biophys. Acta
523
506-515
1978
Bos taurus
brenda
White, A.A.; Zenser, T.V.
Preparation and characterization of guanylate cyclase from bovine lung
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192-195
1974
Bos taurus
brenda
Hakki, S.; Sitaramayya, A.
Guanylate cyclase from bovine rod outer segments: solubilization, partial purification, and regulation by inorganic pyrophosphate
Biochemistry
29
1088-1094
1990
Bos taurus
brenda
Serfass, L.; Burstyn, J.N.
Effect of heme oxygenase inhibitors on soluble guanylyl cyclase activity
Arch. Biochem. Biophys.
359
8-16
1998
Bos taurus
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Mayer, B.; Schrammel, A.; Klatt, P.; Koesling, D.; Schmidt, K.
Peroxynitrite-induced accumulation of cyclic GMP in endothelial cells and stimulation of purified soluble guanylyl cyclase
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29
17355-17360
1995
Bos taurus
brenda
Hayashi, F.; Yamazaki, A.
Polymorphism in purified guanylate cyclase from vertebrate rod photoreceptors
Proc. Natl. Acad. Sci. USA
88
4746-4750
1991
Bos taurus, Rhinella marina, Lithobates catesbeianus
brenda
Koch, K.W.
Purification and identification of photoreceptor guanylate cyclase
J. Biol. Chem.
266
8634-8637
1991
Bos taurus
brenda
Wolbring, G.; Baehr, W.; Palczewski, K.; Schnetkamp, P.P.
Light inhibition of bovine retinal rod guanylyl cyclase mediated by beta gamma-transducin
Biochemistry
38
2611-2616
1999
Bos taurus
brenda
Ivanova, K.; Heim, J.M.; Gerzer, R.
Kinetic characterization of atrial natriuretic factor-sensitive particulate guanylate cyclase
Eur. J. Pharmacol.
189
317-326
1990
Bos taurus
brenda
Schrammel, D.; Koesling, D.; Gorren, A.C.F.; Chevion, M.; Schmidt, K.; Mayer, B.
Inhibition of purified soluble guanylyl cyclase by copper ions
Biochem. Pharmacol.
52
1041-1045
1996
Bos taurus
brenda
Bocanera, L.V.; Martinetto, H.; Flawia, M.M.; Pisarev, M.A.
Partial characterization of guanylyl cyclase activity in calf thyroid
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25
215-228
1999
Bos taurus
brenda
Stone, J.R.; Marletta, M.A.
Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states
Biochemistry
33
5636-5640
1994
Bos taurus
brenda
Aparicio, J.G.; Applebury, M.L.
The bovine photoreceptor outer segment guanylate cyclase: purification, kinetic properties, and molecular size
Protein Expr. Purif.
6
501-511
1995
Bos taurus
brenda
Li, P.L.; Jin, M.W.; Campbell, W.B.
Effect of selective inhibition of soluble guanylyl cyclase on the K(Ca) channel activity in coronary artery smooth muscle
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31
303-308
1998
Bos taurus
brenda
Tomita, T.; Tsuyama, S.; Imai, Y.; Kitagawa, T.
Purification of bovine soluble guanylate cyclase and ADP-ribosylation on its small subunit by bacterial toxins
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122
531-536
1997
Bos taurus
brenda
Horio, Y.; Murad, F.
Purification of guanylyl cyclase from rod outer segments
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1991
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Purification of heme-containing soluble guanylyl cyclase
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1991
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Preparation of soluble guanylyl cyclase from bovine lung by immunoaffinity chromatography
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Molecular and biochemical characterization of a CNP-sensitive guanylyl cyclase in bovine tracheal smooth muscle
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Soluble guanylate cyclases in the retina
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ATP binding is required for physiological activation of retinal guanylate cyclase
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Adenylyl and guanylyl cyclase activity in the choroid
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Purification and characterization of NO-sensitive guanylyl cyclase
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Soluble guanylate cyclase
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Functional characterization of two nucleotide-binding sites in soluble guanylate cyclase
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26
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Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide
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294
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417
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Cardiovascular effects of modulators of soluble guanylyl cyclase activity
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6
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Characterization of oxidized guanosine 5-triphosphate as a viable inhibitor of soluble guanylyl cyclase
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46
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An enzyme-linked receptor mechanism for nitric oxide-activated guanylyl cyclase
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283
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Bos taurus
brenda
Maron, B.A.; Zhang, Y.Y.; Handy, D.E.; Beuve, A.; Tang, S.S.; Loscalzo, J.; Leopold, J.A.
Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells
J. Biol. Chem.
284
7665-7672
2009
Bos taurus
brenda
Behnen, P.; Scholten, A.; Raetscho, N.; Koch, K.W.
The cone-specific calcium sensor guanylate cyclase activating protein 4 from the zebrafish retina
J. Biol. Inorg. Chem.
14
89-99
2009
Bos taurus, Danio rerio
brenda
Mayer, B.; Kleschyov, A.L.; Stessel, H.; Russwurm, M.; Munzel, T.; Koesling, D.; Schmidt, K.
Inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation
Mol. Pharmacol.
75
886-891
2008
Bos taurus
brenda
Kollau, A.; Beretta, M.; Russwurm, M.; Koesling, D.; Keung, W.M.; Schmidt, K.; Mayer, B.
Mitochondrial nitrite reduction coupled to soluble guanylate cyclase activation: lack of evidence for a role in the bioactivation of nitroglycerin
Nitric Oxide
20
53-60
2009
Bos taurus
brenda
Mathis, K.J.; Emmons, T.L.; Curran, D.F.; Day, J.E.; Tomasselli, A.G.
High yield purification of soluble guanylate cyclase from bovine lung
Protein Expr. Purif.
60
58-63
2008
Bos taurus (P16068), Bos taurus (P19687), Bos taurus
brenda
James, L.R.; Griffiths, C.H.; Garthwaite, J.; Bellamy, T.C.
Inhibition of nitric oxide-activated guanylyl cyclase by calmodulin antagonists
Br. J. Pharmacol.
158
1454-1464
2009
Bos taurus
brenda
Makino, R.; Park, S.Y.; Obayashi, E.; Iizuka, T.; Hori, H.; Shiro, Y.
Oxygen binding and redox properties of the heme in soluble guanylate cyclase: implications for the mechanism of ligand discrimination
J. Biol. Chem.
286
15678-15687
2011
Bos taurus
brenda
Makino, R.; Obata, Y.; Tsubaki, M.; Iizuka, T.; Hamajima, Y.; Kato-Yamada, Y.; Mashima, K.; Shiro, Y.
Mechanistic insights into the activation of soluble guanylate cyclase by carbon monoxide a multistep mechanism proposed for the BAY 41-2272 induced formation of 5-coordinate CO-heme
Biochemistry
57
1620-1631
2018
Bos taurus
brenda
Duda, T.; Wen, X.H.; Isayama, T.; Sharma, R.K.; Makino, C.L.
Bicarbonate modulates photoreceptor guanylate cyclase (ROS-GC) catalytic activity
J. Biol. Chem.
290
11052-11060
2015
Bos taurus (O02740), Bos taurus (P55203)
brenda