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D650A
mutation in cyaB1-595-859 catalytical domain, no activity
L259V
affinity for cAMP is at least 11fold higher than for cGMP
more |
replacement of the entire beta1-beta3 region, Ile250 to Ile283, of the cyaB1 GAF B subdomain with Asn411 to Tyr443 of GAF B from rat phosphodiesterase 2, is stimulated by cGMP 10.5fold similar to wild-type cyaB1, whereas activation by cAMP is eliminated, thus switched specificity of the cyaB1 tandem GAF domain from cAMP to cGMP. Swapping of the anterior part, Ile250 to Gly267, in cyaB1 GAF B with Asn411 to Asn426 of rat phosphodiesterase 2, which is stimulated by neither cAMP nor cGMP up to 10 mM. Swapping the C-terminal W270 to I283 section of cyaB1 for Val429 to Tyr443 from rat phosphodiesterase 2 yields a protein that is highly stimulated by both cAMP and cGMP, i.e. purine specificity is lost. Elongation of the swapped stretch of amino acids towards the N-terminal, e.g. when Thr258/Leu259 are included in the domain swapping and replaced by Ser and Val cNMP, specificity is inverted, i.e. the efficacy of cAMP is almost lost, whereas cGMP stimulates cyaB1 AC potently
N728A
mutation in cyaB1-595-859 catalytical domain, no activity
T258S
preference for cGMP over cAMP is 35fold, affinity for both cyclic nucleotides is enhanced
T258S/L259V
response to cGMP is highly diminished
K533E/I603R/D605C
mutant lose adenylyl cyclase activity but obtains significant guanylyl cyclase activity
H351A
-
mutant with no enzyme activity
H351F
-
mutant with 40fold decreased enzyme activity
H351N
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mutant with 34fold decreased enzyme activity
K372A
-
mutant with 30fold reduced catalytic rate constant and 3fold increased Km value for ATP
A225C
a CyaA 1-373 mutant
N347A
-
the mutant shows an enzymatic activity that is reduced by about half as well as 5fold reduced affinity for calmodulin
Q260A/R262A
a CyaA 1-373 mutant, the mutant shows reduced calmodulin-dependent activation of CyaA compared to the wild-type CyaA
Q260C
the mutant shows about 1000fold reduced potency to be activated by calmodulin compared to the wild-type CyaA
R338A/D360A
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the mutant shows no affected catalytic efficiency but 6fold reduced affinity for calmodulin
R338A/N347A/D360A
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the mutant shows 15% of wild type turnover and exhibits 200fold reduced affinity for calmodulin
V1027A/L1031A
is not catalytically active under basal, Galphas- or forskolin-stimulated conditions
D114A
site-directed mutagenesis, the almost inactive mutant shows highly reduced activity compared to the wild-type enzyme
D116A
site-directed mutagenesis, the almost inactive mutant shows highly reduced activity compared to the wild-type enzyme
D300A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
D414B
-
mutant does not show increased cAMP levels
E185A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
E242A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
G463D
-
mutant does not show increased cAMP levels
K136A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
K253A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
K260A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
K264A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
K332A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
R188H
-
mutant does not show increased cAMP levels
R19A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
S103A
site-directed mutagenesis, the mutant has a 17fold higher Km for ATP compared to the wild-type enzyme, and the mutation causes a marked reduction of discrimination between ATP- and ADP- or AMP-derived inhibitors
S106A
site-directed mutagenesis, the mutation reduces the mutant activity to 25% of the wild-type enzyme activity, kinetic analysis show a 58% reduction of the Vmax and a doubling of the Km compared to the wild-type enzyme
S113A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
T189A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
W118A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
W200A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
W249A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
W374A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
Y394A
site-directed mutagenesis, the mutant shows reduced Vmax and altered Km compared to the wild-type enzyme
F1078S
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isoform VI, mutation within the GALPHAS binding pocket
N1090D
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isoform V, mutation within the GALPHAS binding pocket
N955A
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mutation prevents glycosylation
N964A
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mutation prevents glycosylation
Y1082L
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mutation in AC9 confers both binding and activation by forskolin
D147A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1647 mutant, mutation of first metal-binding residue, barely active
D241C
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity
D256A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of the metal-binding residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
D256A/D300A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 mixture of artificial C2-like mutants of Rv1625c, reconstitutes an active enzyme
D300A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of the metal-binding residue, leads to significant decrease in adenylyl cyclase activity, can heterodimerize and reconstitute activity with the Paramaecium guanylyl cyclase C1-like domain, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
D365A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of the substrate specifying residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
E136A
shift of the pH optimum by about 0.5 unit to acidic pH
E136R
shift of the pH optimum by about 0.5 unit to acidic pH
E195A
mutation with partially relieved inhibition and 4fold increased enzyme activity at pH 8.0, pH optimum shifted from 5.8 to 6.5
H103A
pH regulation is barely affected, not involved in pH-regulation
H140A
pH regulation is barely affected, not involved in pH-regulation, shift of the pH optimum by about 0.5 unit to acidic pH
H140R
inhibition is relaxed slightly, with a shift of the pH optimum toward more basic values
H192A
mutant with wild-type phenotype at pH 8.0, the slope of activation is shifted by 0.5 pH units towards the acidic pH. 10fold higher enzyme activity at pH 8.0 than the wild type
H58A
pH regulation is barely affected, not involved in pH-regulation
K187E
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity
K187E/D241C
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1647 mutant, mixture of artificial C1-like mutants, reconstitutes high adenylyl cyclase activity, does not lead to a gain in guanylyl cyclase activity
K296A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of the substrate specifying residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
K296A/D365A/R376A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 mixture of artificial C1-like mutants of Rv1625c, reconstitutes an active enzyme
Q57K/N106D
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv0386 mutant, abolishes activity
R132A
shift of the pH optimum by about 0.5 unit to acidic pH
R132E
results in a biphasic pH activity curve with a minimum at pH 6.5 and higher activity at basic pH values
R18A
88% of wild-type activity, in the presence of 2 mM Mn2+
R18A/R19G
67% of wild-type activity, in the presence of 2 mM Mn2+
R19G
78% of wild-type activity, in the presence of 2 mM Mn2+
R27A
78% of wild-type activity, in the presence of 2 mM Mn2+
R309A
mutation renders holoenzyme active and unregulated
R31G
118% of wild-type activity, in the presence of 2 mM Mn2+
R376A
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of the transition state stabilizing residue, leads to significant decrease in adenylyl cyclase activity
R43A
61% of wild-type activity, in the presence of 2 mM Mn2+
R43K
77% of wild-type activity, in the presence of 2 mM Mn2+
R43K/R44K
39% of wild-type activity, in the presence of 2 mM Mn2+
R44G
41% of wild-type activity, in the presence of 2 mM Mn2+
R44K
116% of wild-type activity, in the presence of 2 mM Mn2+
R46A
85% of wild-type activity, in the presence of 2 mM Mn2+
R46K
135% of wild-type activity, in the presence of 2 mM Mn2+
R4G
77% of wild-type activity, in the presence of 2 mM Mn2+
D147A
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Rv1647 mutant, mutation of first metal-binding residue, barely active
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D241C
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Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity
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D256A
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Rv1625c mutant, mutation of the metal-binding residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
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D365A
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Rv1625c mutant, mutation of the substrate specifying residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647
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D365C
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Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity
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E136A
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shift of the pH optimum by about 0.5 unit to acidic pH
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E195A
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mutation with partially relieved inhibition and 4fold increased enzyme activity at pH 8.0, pH optimum shifted from 5.8 to 6.5
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F363R
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mutant with poor adenylate cyclase acitivity
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H140A
-
pH regulation is barely affected, not involved in pH-regulation, shift of the pH optimum by about 0.5 unit to acidic pH
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H140R
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inhibition is relaxed slightly, with a shift of the pH optimum toward more basic values
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H192A
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mutant with wild-type phenotype at pH 8.0, the slope of activation is shifted by 0.5 pH units towards the acidic pH. 10fold higher enzyme activity at pH 8.0 than the wild type
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K187E
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Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity
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K187E/D241C
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Rv1647 mutant, mixture of artificial C1-like mutants, reconstitutes high adenylyl cyclase activity, does not lead to a gain in guanylyl cyclase activity
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K296E/D365C
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double mutant with severely compromised enzyme activity
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K296E/F363R/D365C
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triple mutant with severely compromised enzyme activity
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Q57K/N106D
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Rv0386 mutant, abolishes activity
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R132A
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shift of the pH optimum by about 0.5 unit to acidic pH
-
R18A
-
88% of wild-type activity, in the presence of 2 mM Mn2+
-
R19G
-
78% of wild-type activity, in the presence of 2 mM Mn2+
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R27A
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78% of wild-type activity, in the presence of 2 mM Mn2+
-
R309A
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mutation renders holoenzyme active and unregulated
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R43A/R44G
-
1.3% of wild-type activity, in the presence of 2 mM Mn2+
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R4G
-
77% of wild-type activity, in the presence of 2 mM Mn2+
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D200N
mutant shows no activation on light exposure
F197S
mutant shows no activation on light exposure
L111A/L115A
mutant shows no activation on light exposure
N256A
mutant shows no activation on light exposure
Y125A
mutant shows no activation on light exposure
D200N
-
mutant shows no activation on light exposure
-
F197S
-
mutant shows no activation on light exposure
-
L111A/L115A
-
mutant shows no activation on light exposure
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N256A
-
mutant shows no activation on light exposure
-
Y125A
-
mutant shows no activation on light exposure
-
A197T
the mutant shows increased activity compared to the wild type enzyme
D212N
-
mutant with no detectable enzyme activity
D214N
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mutant with no detectable enzyme activity
E189R
the mutant shows increased activity compared to the wild type enzyme
E377G
the mutant shows increased activity compared to the wild type enzyme
F399H
the mutant shows increased activity compared to the wild type enzyme
F399I
the mutant shows increased activity compared to the wild type enzyme
I352T
the mutant shows increased activity compared to the wild type enzyme
K274A
-
the mutation significantly reduces adenylate cyclase activity
K81M
-
mutant with no detectable enzyme activity
K88I
-
mutant with no detectable enzyme activity
L326P
the mutant shows increased activity compared to the wild type enzyme
r23ExoY
-
mutant with histidine tag at carboxyl-terminal position, detectable enzyme activity
R318W
the mutant shows increased activity compared to the wild type enzyme
R412H
the mutant shows slightly increased activity compared to the wild type enzyme
R456L
the mutant shows strongly increased activity compared to the wild type enzyme
rExoY
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mutant with histidine tag at amino-terminal position, detectable enzyme activity
T351A
-
the mutation significantly reduces adenylate cyclase activity
E189R
-
the mutant shows increased activity compared to the wild type enzyme
-
E377G
-
the mutant shows increased activity compared to the wild type enzyme
-
F399I
-
the mutant shows increased activity compared to the wild type enzyme
-
L326P
-
the mutant shows increased activity compared to the wild type enzyme
-
R318W
-
the mutant shows increased activity compared to the wild type enzyme
-
K274A
-
the mutation significantly reduces adenylate cyclase activity
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T351A
-
the mutation significantly reduces adenylate cyclase activity
-
D396A
-
almost no activity
D396A/D440A
-
no activity
D396A/D440N
-
no activity
D396N
-
almost no activity
D396N/D440A
-
no activity
D396N/D440N
-
no activity
D425A
-
catalytically inactive mutant of isoform AC6, the expression of the mutant is associated with marked reduction in cAMP production
D440A
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almost no activity
D440N
-
almost no activity
K1876M
-
large decrease in cAMP signalling
C83A
Q7CH76
the mutation results in moderate to sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
D143A
-
does not crystallize
D55K
Q7CH76
the mutant shows increased Km for Mg2+ compared to the wild type enzyme
E10Q
Q7CH76
the mutation results in about 8fold reduction in activity with 20 mM Mg2+ and in a 5fold increase in activity in the presence of 10 mM Mn2+
E12Q
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
E84A
-
gives crystals that are unsuitable owing to poor crystal growth or poor diffraction
F5A
Q7CH76
the mutant shows increased Km for Mg2+ compared to the wild type enzyme
K14A
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
K76A
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
L72A
Q7CH76
the mutant shows about 2fold increased Km for Mg2+ compared to the wild type enzyme
M140A
Q7CH76
the mutation results in moderate to sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
R113A
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ and no activity with Mg2+
R63A
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
E497K/C566D
mutations within the nucleotide binding site generates rhodopsin-adenylyl cyclases
E497K/C566D
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mutations within the nucleotide binding site generates rhodopsin-adenylyl cyclases
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D365C
-
0.06% of wild-type activity, mutant displays classical Michaelis-Menten kinetics, in contrast to the sigmoidal kinetics of the wild-type
D365C
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity
F363R
mutant with poor adenylate cyclase acitivity
F363R
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity
K296E
-
0.5% of wild-type activity, mutant displays classical Michaelis-Menten kinetics, in contrast to the sigmoidal kinetics of the wild-type
K296E
mutant with about 400fold reduced enzyme activity
K296E
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity
K296E/D365C
-
0.025% of wild-type activity, mutant displays classical Michaelis-Menten kinetics, in contrast to the sigmoidal kinetics of the wild-type
K296E/D365C
double mutant with severely compromised enzyme activity
K296E/F363R/D365C
-
0.5% of wild-type activity, mutant displays classical Michaelis-Menten kinetics, in contrast to the sigmoidal kinetics of the wild-type
K296E/F363R/D365C
triple mutant with severely compromised enzyme activity
K296E/F363R/D365C
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, is largely monomeric, has neither adenylyl cyclase or guanylyl cyclase activity, unable to heterodimerize with the wild-type protein
R43A/R44G
1.3% of wild-type activity, in the presence of 2 mM Mn2+
R43A/R44G
O06362, O06572, O07732, O53213, O53720, P71914, P94982, P9WM05, P9WMU7, P9WMV1, P9WQ29, P9WQ31, P9WQ33, P9WQ35, Q11028 Rv1625c mutant, mutation of two arginine residues in the extreme N-terminal region, preceding the first transmembrane helix, severely compromises adenylyl activity of the full length protein
K296E
-
mutant with about 400fold reduced enzyme activity
-
K296E
-
Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity
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E10A
-
gives crystals that are unsuitable owing to poor crystal growth or poor diffraction
E10A
Q7CH76
the mutation results in about 8fold reduction in activity with 20 mM Mg2+ and in a 5fold increase in activity in the presence of 10 mM Mn2+
E136A
-
gives crystals that are unsuitable owing to poor crystal growth or poor diffraction
E136A
Q7CH76
the mutation results in sharp decreases in activity in the presence of 10 mM Mn2+ or 20 mM Mg2+
additional information
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mutation of either His572 or Asp895 greatly reduces AC activity
additional information
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downregulation of the cyaA gene leads to reduced virulence of the organism, e.g. strain 253, in C57BL/6 mice, overview. The cya locus, which encodes, activates, and secretes CyaA, is replaced by an operon ptp, predicted to encode peptide transport proteins, in strain 253, genotyping and phylogenetic analysis, overview
additional information
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mutants lacking either filamentous haemagglutinin or ACT (strain Bp3183) show significantly decreased adherence to human epithelial respiratory cells, lack of ACT does not affect filamentous haemagglutinin cellular expression, attachment level of the ACT-deficient mutant to A549 cells is not affected by the presence of heparin
additional information
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CyaA causes similar morphological changes in various cultured cell lines: L2, EBL, HEK293T, MC3T3-E1, NIH 3T3, and Vero cells are rounded by the toxin whereas Caco-2, Eph4, and MDCK cells are not, although all these cells show a significant elevation of the intracellular cAMP level in response to CyaA treatment. An inactive enzyme mutant does not cause cell form modifications in infected rats in contrast to the wild-type enzyme, overview
additional information
the CyaA mutant with a Cys/Thr insertion at amino acids 188/189 is unable to kill J774 mouse macrophage-like cells at a concentration as high as 0.010 mg/ml, yet lytic activity towards erythrocytes is retained. Binding of a monoclonal antibody distal to the inactivated catalytic site restored cytotoxicity towards J774 cells and further enhances haemolytic activity, construction of mutant CyaA* lacking adenylate cyclase enzymatic activity, and of non-acylated forms of wild-type CyaA and mutant CyaA*, proCyaA and proCyaA*, CyaA* is as cytotoxic towards J774.2 cells as CyaA and mediates cell killing at a faster rate than CyaA at higher concentration than 0.0001 mg/ml. Non-acylated mutant proCyaA* has no detectable cytotoxic or apoptotic activity. A 500fold higher concentration of non-acylated or mutant CyaA is necessary for inhibition of the zymosan-stimulated oxidative burst
additional information
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the CyaA mutant with a Cys/Thr insertion at amino acids 188/189 is unable to kill J774 mouse macrophage-like cells at a concentration as high as 0.010 mg/ml, yet lytic activity towards erythrocytes is retained. Binding of a monoclonal antibody distal to the inactivated catalytic site restored cytotoxicity towards J774 cells and further enhances haemolytic activity, construction of mutant CyaA* lacking adenylate cyclase enzymatic activity, and of non-acylated forms of wild-type CyaA and mutant CyaA*, proCyaA and proCyaA*, CyaA* is as cytotoxic towards J774.2 cells as CyaA and mediates cell killing at a faster rate than CyaA at higher concentration than 0.0001 mg/ml. Non-acylated mutant proCyaA* has no detectable cytotoxic or apoptotic activity. A 500fold higher concentration of non-acylated or mutant CyaA is necessary for inhibition of the zymosan-stimulated oxidative burst
additional information
upon insertion of the N-terminal adenylyl cyclase domain of Bordetella pertussis CyaA to its targeted eukaryotic cells, target cell calmodulin binds to this domain tightly with high affinity, the interaction activates the adenylyl cyclase activity of CyaA leading to a rise in intracellular cAMP levels to disrupt normal cellular signaling, the complex formation between N-CaM and CyaA contributes a 400fold increase of binding affinity between CyaA and CaM
additional information
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upon insertion of the N-terminal adenylyl cyclase domain of Bordetella pertussis CyaA to its targeted eukaryotic cells, target cell calmodulin binds to this domain tightly with high affinity, the interaction activates the adenylyl cyclase activity of CyaA leading to a rise in intracellular cAMP levels to disrupt normal cellular signaling, the complex formation between N-CaM and CyaA contributes a 400fold increase of binding affinity between CyaA and CaM
additional information
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mutants lacking either filamentous haemagglutinin or ACT (strain Bp3183) show significantly decreased adherence to human epithelial respiratory cells, lack of ACT does not affect filamentous haemagglutinin cellular expression, attachment level of the ACT-deficient mutant to A549 cells is not affected by the presence of heparin
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additional information
ACI-deletion mutants ACI.lambda1057 with reduced catalytic activity and ACI.lambda1094, which like mutant ACIlambda1057 is active and stimulated by Ca/CaM as well as ACI. Mutant ACII.lambda928 is catalytically inactive, mutant ACII.AA930 shows diminished activity, mutants ACII.AA925 or ACII.AA932 show no significant change in Gbetagamma-regulation
additional information
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construction of a mutant strain expressing a version of Cyr1p with an N-terminal His-Flag-Myc tag under the control of the MET3 promoter
additional information
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aca-/rdeA- mutant cells with significant activity of ACB, which is not obscured by the presence of ACA, aca-/A15::ACG mutant cells, which express ACG
additional information
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deletion of a 12TM domain of ACA, does not perturb cAMP secretion
additional information
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RNAi against gene AC78C, but not against gene ACXE, depressed the sucrose response in gustatory receptor neurons
additional information
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the learning mutant rutabaga, i.e. rut, shows reduced synaptic strength and precision compared to the wild-type enzyme, rut motor terminals display greatly increased variability among corresponding terminal branches of different larval neuromuscluar junctions of different samples, defects in rut adenylyl cyclase results in reduced Ca2+ currents in the nerve terminal, phenotype, overview
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AC7AC3 chimeric mutants, exchange of the putative transmembrane domains, M1 and M2 or of the N-terminal tail has no effect on the ethanol response of enzyme activity
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mutant ACVIdeltaN, shows a much lower activity as compared with full-length ACVI, but its stimulated activity is about 4fold higher than the corresponding control activity, activities of the recombinant, engineered, soluble forms of ACV and ACVI, which lack the N termini, are not enhanced by Gbetagamma subunits. Deletion of residues 77-151, but not 1-76, in the N-terminal region of ACVI obliterates the ability of Gbetagamma subunits to conditionally stimulate the enzyme
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construction of various truncated versions of isozyme AC6 lacking parts of the C-terminal domains C1 or C2, localization of the structural features required for interaction with lipid rafts, overview
additional information
RNAi is used to knockdown each of the four AC isozymes AC2, AC3, AC7, and AC9 specifically and individually in RAW 264.7 cells, bone marrow-derived macrophage from AC7 knockout mice are devoid of an sphingosine 1-phosphate effect on cAMP stimulated by Gs-dependent pathways, but exogenous expression of AC7, while not of AC2, is sufficient to recapitulate the sphingosine 1-phosphate/G13 effect on intracellular cAMP responses. Regulation of the Gs-stimulated cAMP responses by the Gi and Gq/Ca2+ pathways is affected in AC7-deficient cells, overview
additional information
RNAi is used to knockdown each of the four AC isozymes AC2, AC3, AC7, and AC9 specifically and individually in RAW 264.7 cells, bone marrow-derived macrophage from AC7 knockout mice are devoid of an sphingosine 1-phosphate effect on cAMP stimulated by Gs-dependent pathways, but exogenous expression of AC7, while not of AC2, is sufficient to recapitulate the sphingosine 1-phosphate/G13 effect on intracellular cAMP responses. Regulation of the Gs-stimulated cAMP responses by the Gi and Gq/Ca2+ pathways is affected in AC7-deficient cells, overview
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sixteen single-nucleotide polymorphisms distributed throughout the ADCY10 gene are genotyped in two healthy groups of American whites: 1692 premenopausal women and 715 men, genotype association with bone mineral density phenotypes, overview
additional information
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AC5-/- mice, all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated. Sniffing, ptosis, teeth chattering, and body tremor are markedly reduced, diarrhea and paw tremor are not significantly different, the number of jumps is dramatically increased. Behavioral effects of selective micro or delta opioid receptor agonists are lost, behavioral effects of selective kappa opioid receptor agonists are unaffected. Loss of AC5 does not alter expression levels of opioid receptor transcripts
additional information
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AC5-deficient (AC5-/-) mice, reduction of basal L-type Ca2+ currents is significantly less pronounced than in wild-type myocytes, isoproterenol effects on L-type Ca2+ currents are mitigated
additional information
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deletion of sAC, leads to inhibition of sperm mobility, animals are infertile, AC3 knockout mice, exhibit peripheral and behavioral anosmia
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homozygous mutants AC1KO, AC8KO and AC1/AC8KO
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knockout of sAC in mice causes male sterility by impaired sperm motility, while spermatogenesis is not affected
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mice deficient in AC1, are resistant to glutamate-induced neuronal toxicity, double knock-out AC1 and AC8 mice, show long lasting long-term potentiation and memory deficits that are greater in animals lacking both AC1 and AC8, when compared to animals deficient in only a single isoform. Behavioral responses to inflammatory stimuli that appear to involve N-methyl-D-aspartate receptor pathways are markedly reduced in double knockouts and AC1-/- mice. AC1-/- mice are resistant to glutamate-induced neuronal toxicity
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mice with collecting duct-specific deletion of endothelin-1, mRNA or protein levels of AC3 not affected, increased protein levels of AC5/6, AC5 and AC6 mRNA levels are unchanged, show enhanced vasopressin-stimulated cAMP accumulation
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sAC-/- spermatozoa, adenylyl cyclase activity and cAMP content are greatly diminished and are undetectable after sperm purification. HCO3- is unable to rapidly accelerate the flagellar beat or facilitate evoked Ca2+ entry into sAC-/- spermatozoa. However, sAC-/- sperm fertilize zona-free oocytes
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AC1 mutant mouse, barrelless, lacks typical barrel cytoarchitecture, and displays presynaptic and postsynaptic functional defects at thalamocortical synapses, in which LTP induction and the developmental increase in AMPA receptor response at thalamocortical synapses are impaired. The barrel cortex phenotype of brl mice may be a consequence of AC1 disruption in cortical or subcortical regions
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AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
AC8 knockout mice show decreased Ca2+ -stimulated adenylate cyclase activity in the hippocampus, hypothalamus, thalamus, and brainstem, and exhibit little or no mossy fiber LTP, i.e. long-term potentiation, the long-lasting enhancement in communication between two neurons that results from stimulation. Short-term plasticity is also impaired in AC8 knockout mice. Double knockouts of both isozymes AC1 and AC8 also exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
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Adcy1-/- mice lack the type 1 adenylyl cyclase, no compensatory changes in the levels of transcripts encoding the related type 8 adenylyl cyclase isoform in retinas of mice deficient in AC1, phenotype of AC1-deficient mice, overview. A dysfunction of Ca2+/CaM-stimulated adenylyl cyclase activity in Drd4-/-mouse retina appears to be due primarily to low levels of expression of the AC1 and not to changes in CaM expression
additional information
construction of a chimeric mutant dimer of AC2/AC5, which shows increased activation by GalphaS proteins as compared to the single isozymes AC2 and AC5, expression of the chimeric dimer elevates cAMP production in transfected cells 6fold, while that of the single isozymes each cause a 2fold increase in cAMP production, overview
additional information
construction of a chimeric mutant dimer of AC2/AC5, which shows increased activation by GalphaS proteins as compared to the single isozymes AC2 and AC5, expression of the chimeric dimer elevates cAMP production in transfected cells 6fold, while that of the single isozymes each cause a 2fold increase in cAMP production, overview
additional information
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construction of a chimeric mutant dimer of AC2/AC5, which shows increased activation by GalphaS proteins as compared to the single isozymes AC2 and AC5, expression of the chimeric dimer elevates cAMP production in transfected cells 6fold, while that of the single isozymes each cause a 2fold increase in cAMP production, overview
additional information
construction of AC1 and AC1/8 double knockout mice, AC1 knockout mice exhibit reduced opiate, e.g. morphine, dependence on the basis of attenuated withdrawal, however, partially distinct withdrawal symptoms are affected in the two lines. The ability of chronic morphine to enhance the effect of forskolin on LC firing rates is completely abolished in AC8 and AC1/8 deficient mutants, morphine regulation of gene expression in locus coeruleus of AC1 KO mice, overview
additional information
construction of AC1 and AC1/8 double knockout mice, AC1 knockout mice exhibit reduced opiate, e.g. morphine, dependence on the basis of attenuated withdrawal, however, partially distinct withdrawal symptoms are affected in the two lines. The ability of chronic morphine to enhance the effect of forskolin on LC firing rates is completely abolished in AC8 and AC1/8 deficient mutants, morphine regulation of gene expression in locus coeruleus of AC1 KO mice, overview
additional information
construction of AC8 knockout and AC1/8 double knockout mice, that exhibit reduced opiate, e.g. morphine, dependence on the basis of attenuated withdrawal, however, partially distinct withdrawal symptoms are affected in the two lines. The ability of chronic morphine to enhance the effect of forskolin on LC firing rates is completely abolished in AC8 and AC1/8 deficient mutants, morphine regulation of gene expression in locus coeruleus of AC8 KO mice, overview
additional information
construction of AC8 knockout and AC1/8 double knockout mice, that exhibit reduced opiate, e.g. morphine, dependence on the basis of attenuated withdrawal, however, partially distinct withdrawal symptoms are affected in the two lines. The ability of chronic morphine to enhance the effect of forskolin on LC firing rates is completely abolished in AC8 and AC1/8 deficient mutants, morphine regulation of gene expression in locus coeruleus of AC8 KO mice, overview
additional information
construction of male and female AC1/8 double knockout mice and AC5 knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC1/8 double knockout mice and AC5 knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC1/8 double knockout mice and AC5 knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC1/8 double knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC1/8 double knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC1/8 double knockout mice. AC1/AC8 double knockout mice are hypoactive, exhibit diminished sucrose preference, and display alterations in neurotrophic signaling, generally consistent with a prodepressant phenotype. Neither line of mice display alterations in hippocampal cell proliferation, but altered BDNF signaling, phenotypes, overview
additional information
construction of male and female AC5 knockout mice. AC5KO mice show striking anxiolytic and antidepressant phenotypes on standard behavioral assays, phenotype, overview
additional information
construction of male and female AC5 knockout mice. AC5KO mice show striking anxiolytic and antidepressant phenotypes on standard behavioral assays, phenotype, overview
additional information
construction of male and female AC5 knockout mice. AC5KO mice show striking anxiolytic and antidepressant phenotypes on standard behavioral assays, phenotype, overview
additional information
construction of sAC knock-out mice containing an internal ribosome entry site-LacZ/neomycin cassette that replaces exons 2-4, deleting sequence encoding a portion of the C1 domain of sAC, the C1 domain combines with C2 to form the cyclase catalytic domain. RNA transcription proceeds through the inserted IRES-LacZ/neomycin cassette and mRNAencoding C2 is produced, but not the C1 region in testis of adult sAC-null mice, but due to the frameshift of the transgene intro the C2 portions of sAC are not translated and neither sAC protein nor its activity are detectable in testis and spermatozoa of knock-out animals, overview. sAC-null mice do not exhibit any obvious neurological deficits
additional information
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double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
double knockouts of both isozymes AC1 and AC8 exhibit a nearly complete loss of mossy fiber long-term potentiation
additional information
generation of transgenic mice with disrupted AC5 or overexpressing AC5, the latter type shows less decreased heart rate in later phases within one parabola, the inverse heart rate is more variable in AC5 knockout mice and less variable in AC5 overexpressing mice compared to wild-type mice, overview
additional information
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generation of transgenic mice with disrupted AC5 or overexpressing AC5, the latter type shows less decreased heart rate in later phases within one parabola, the inverse heart rate is more variable in AC5 knockout mice and less variable in AC5 overexpressing mice compared to wild-type mice, overview
additional information
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genetic disruption of adenylyl cyclase type 5 in mice leads to one-third longer live spans of the mutant mice compared to the wild-type mice, and protection from aging-induced, pressure overload-induced and catecholamine-induced stresses, AC5 KO mice are protected from the osteoporosis of aging, overview
additional information
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in cells from mice doubly deficient in isozymes AC1 and AC8, the baseline percentage of active synapses is only modestly reduced compared with wild-type synapses, and forskolin unsilencing is similar in the two genotypes, but after strong presynaptic silencing, recovery of normal function is strongly inhibited in AC1/AC8-deficient synapses, the entire recovery phenotype of the double null is reproduced in AC8-deficient but not in AC1-deficient cells, overview
additional information
increase of Fmr1 mRNA is attenuated in ACC slices from AC1 KO mice compared to wild-type mice, and induced phosphorylation of CREB is significantly attenuated in ACC slices from AC1 KO mice compared with WT mice
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increase of Fmr1 mRNA is attenuated in ACC slices from AC1 KO mice compared to wild-type mice, and induced phosphorylation of CREB is significantly attenuated in ACC slices from AC1 KO mice compared with WT mice
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mice lacking AC5 display strong reductions in anxiety-like behavior in several paradigms. This anxiolytic behavior in AC5-deficient mice is reduced by the D1 receptor antagonist SCH23390 and enhanced by the D1 dopamine receptor agonist, dihydrexidine or DHX. DHX-stimulated c-fos induction was enhanced in the dorso-medial striatum and NAc in AC5-deficient mice, phenotype, overview. siRNA-mediated inhibition of AC5 levels within the NAc is sufficient to produce an anxiolytic-like response, causing upregulation of prodynorphin and downregulation of cholecystokinin in the NAc of AC5-deficient mice, the effect is reversible by administration of nor-binaltorphimine, a kappa opioid receptor antagonist, or CCK-8s, a CCK receptor agonist, overview
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mice overexpressing AC1 show superior remote contextual memory even though they exhibit normal hippocampus-dependent contextual memory, AC1 knockout mice show lower remote memory 11 weeks, but not within the first 5 weeks, after training compared with wild-type mice, phenotypes, overview
additional information
sperm from Sacy null mice are immotile or weakly motile, but their motility is activated by the cAMP analogues N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate acetoxymethyl ester activated motility. Ca2+ cannot substitute for cAMP analogues in activating motility in the mutant, overview
additional information
the basal phosphorylation levels of CREB are not changed in ACC slices from AC8 KO mice
additional information
the basal phosphorylation levels of CREB are not changed in ACC slices from AC8 KO mice
additional information
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the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC1 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, phenotypes, overview
additional information
the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC1 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, phenotypes, overview
additional information
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the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC8 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, isozyme AC8 KO mice display more dramatic impairments for the improvement in escape latency, saving time, and trial numbers needed to reach the escape latency criterion of 20 s compared to wild-type mice, phenotypes, overview
additional information
the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC8 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, isozyme AC8 KO mice display more dramatic impairments for the improvement in escape latency, saving time, and trial numbers needed to reach the escape latency criterion of 20 s compared to wild-type mice, phenotypes, overview
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transgenic mice that express a mutant, constitutively active inhibitory G protein, Galpha12, in principal neurons of the forebrain, show markedly enhanced long-term depression and impaired late-phase long-term potentiation at Schaffer collateral synapses, with no associated differences in input/output relations, paired-pulse facilitation, or NMDA receptor-gated conductances
additional information
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Adcy1-/- mice lack the type 1 adenylyl cyclase, no compensatory changes in the levels of transcripts encoding the related type 8 adenylyl cyclase isoform in retinas of mice deficient in AC1, phenotype of AC1-deficient mice, overview. A dysfunction of Ca2+/CaM-stimulated adenylyl cyclase activity in Drd4-/-mouse retina appears to be due primarily to low levels of expression of the AC1 and not to changes in CaM expression
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additional information
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AC5-/- mice, all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated. Sniffing, ptosis, teeth chattering, and body tremor are markedly reduced, diarrhea and paw tremor are not significantly different, the number of jumps is dramatically increased. Behavioral effects of selective micro or delta opioid receptor agonists are lost, behavioral effects of selective kappa opioid receptor agonists are unaffected. Loss of AC5 does not alter expression levels of opioid receptor transcripts
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additional information
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AC5-deficient (AC5-/-) mice, reduction of basal L-type Ca2+ currents is significantly less pronounced than in wild-type myocytes, isoproterenol effects on L-type Ca2+ currents are mitigated
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additional information
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homozygous mutants AC1KO, AC8KO and AC1/AC8KO
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additional information
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the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC1 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, phenotypes, overview
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additional information
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generation of transgenic mice with disrupted AC5 or overexpressing AC5, the latter type shows less decreased heart rate in later phases within one parabola, the inverse heart rate is more variable in AC5 knockout mice and less variable in AC5 overexpressing mice compared to wild-type mice, overview
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additional information
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the Ca2+-stimulated enzyme activity is significantly reduced in the hippocampus of isozyme AC8 KO mice and totally lost in double-knockout AC1/AC8 mutant mice, isozyme AC8 KO mice display more dramatic impairments for the improvement in escape latency, saving time, and trial numbers needed to reach the escape latency criterion of 20 s compared to wild-type mice, phenotypes, overview
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additional information
from Ala232 N-terminal truncated mutant has much lower enzyme activity compared with the wild type, significant reduction in the apparent Vmax with no appreciable change in the apparent K' for ATP
additional information
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from Ala232 N-terminal truncated mutant has much lower enzyme activity compared with the wild type, significant reduction in the apparent Vmax with no appreciable change in the apparent K' for ATP
additional information
deletion in the shoulder domain of the holoenzyme, linking of the two adjoining Calpha positions of residues Ala93 and His103, which are 4.6 A apart, mutant enzyme is 7fold more active at pH 8.0 compared to the wild-type enzyme, and shows only a residual 3fold activation at pH 5.5. When the entire shoulder domain is deleted, residues Asp62 to Arg105, the phenotype is similar. This deletion joins the Calpha positions of residues Gly61 and Ala106, which are 6.4 A apart in the wild-type structure
additional information
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deletion in the shoulder domain of the holoenzyme, linking of the two adjoining Calpha positions of residues Ala93 and His103, which are 4.6 A apart, mutant enzyme is 7fold more active at pH 8.0 compared to the wild-type enzyme, and shows only a residual 3fold activation at pH 5.5. When the entire shoulder domain is deleted, residues Asp62 to Arg105, the phenotype is similar. This deletion joins the Calpha positions of residues Gly61 and Ala106, which are 6.4 A apart in the wild-type structure
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
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knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
mutation of N342 does not affect adenylyl cyclase activity in Rv1900c
additional information
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from Ala232 N-terminal truncated mutant has much lower enzyme activity compared with the wild type, significant reduction in the apparent Vmax with no appreciable change in the apparent K' for ATP
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additional information
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knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection
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additional information
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deletion in the shoulder domain of the holoenzyme, linking of the two adjoining Calpha positions of residues Ala93 and His103, which are 4.6 A apart, mutant enzyme is 7fold more active at pH 8.0 compared to the wild-type enzyme, and shows only a residual 3fold activation at pH 5.5. When the entire shoulder domain is deleted, residues Asp62 to Arg105, the phenotype is similar. This deletion joins the Calpha positions of residues Gly61 and Ala106, which are 6.4 A apart in the wild-type structure
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additional information
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disruption of the catalytic domain of CyaC significantly increases symbiotic competency with the symbiotic partner Blasia pusilla, whereas reduced infectivity is observed in a mutant disrupted close to the 6 N-terminus of CyaC. Total cellular cAMP levels are significantly reduced in both mutants
additional information
deletion of CyaC reduces cellular cAMP levels to 25% of wild-type, in the mutant cells cAMP levels are not lowered by light as in wild-type cells, but stay constant
additional information
deletion of CyaC reduces cellular cAMP levels to 25% of wild-type, in the mutant cells cAMP levels are not lowered by light as in wild-type cells, but stay constant
additional information
deletion of CyaC reduces cellular cAMP levels to 25% of wild-type, in the mutant cells cAMP levels are not lowered by light as in wild-type cells, but stay constant
additional information
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generation of Plasmodium berghei parasites deficient in adenylyl cyclase alpha, ACa. The ACalpha-deficient sporozoites do not exocytose in response to migration through host cells and present more than 50% impaired hepatocyte infectivity in vivo compared to wild-type parasites, phenotype, overview
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disruption of a class IIIb AC gene results in strong attenuation
additional information
AC7-AC2 chimeric mutants, regardless of the origin of the N-terminal tail, C1b, M1, and M2 domains, the ethanol response of the mutant is similar to that of the parent isoform of AC, from which the C1a and C2 domains are derived
additional information
AC7-AC2 chimeric mutants, regardless of the origin of the N-terminal tail, C1b, M1, and M2 domains, the ethanol response of the mutant is similar to that of the parent isoform of AC, from which the C1a and C2 domains are derived
additional information
AC7AC3 chimeric mutants, exchange of the putative transmembrane domains, M1 and M2 or of the N-terminal tail has no effect on the ethanol response of enzyme activity
additional information
AC7AC3 chimeric mutants, exchange of the putative transmembrane domains, M1 and M2 or of the N-terminal tail has no effect on the ethanol response of enzyme activity
additional information
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genetic deletion of the second through fourth coding exons in Sacytm1Lex/Sacytm1Lex knockout mice, deficient in sperm soluble isozyme, results in a male sterile phenotype, the soluble isozymes from brain are not affected, overview
additional information
RNA interference knockdown of soluble adenylyl cyclase in mpkCCDc14 cells leads to a yield of about 60% knockdown of the predominant somatic soluble adenylyl cyclase isoforms of 50-53 kDa, also amiloride-sensitive Isc is inhibited to a comparable extent
additional information
construction and phenotypic characterization of a DELTAsac1 disruption strain, construction of single knockout mutants of the genes gsa and sac1, and DELTAgsa/DELTAsac1 double mutants and one DELTAgsa2/DELTAgsa3/DELTAsac1 triple mutant, phenotypes. While the single mutants show some reduction of fertility, double mutants DELTAgsa1/DELTAgsa2 and DELTAgsa1/DELTAgsa3 are completely sterile, overview
additional information
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construction and phenotypic characterization of a DELTAsac1 disruption strain, construction of single knockout mutants of the genes gsa and sac1, and DELTAgsa/DELTAsac1 double mutants and one DELTAgsa2/DELTAgsa3/DELTAsac1 triple mutant, phenotypes. While the single mutants show some reduction of fertility, double mutants DELTAgsa1/DELTAgsa2 and DELTAgsa1/DELTAgsa3 are completely sterile, overview
additional information
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strain lacking the Rv1264-like cyclase is unable to execute an apparently cAMP and acid pH-dependent differentiation pathway
additional information
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truncated version of Cya1 consisting of amino acids 95 to 338, mutant with significant lower specific activity