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A416T
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inactive mutant protein
A416V
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inactive mutant protein
A417G
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the mutant enzyme converts arachidonic acid to (11R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid and (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid in a 1.5:1 ratio. The wild.type enzyme converts arachidonic acid exlusively (15S)-Hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid. Turnover number for arachidonic acid is 4.6fold lower than that of the wild-type enzyme, no significant change in Km-value
D602Y
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15-LOX-2 mutant shows a similar pH-profile as the wild-type enzyme
D602Y/V603H
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a strong shift of the pH profile of 15-LOX-2 mutant towards more acidic values
H361L
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is devoid of enzymatic activity, can induce phosphorylation of p53 as the wild-type
I417A
naturally occuring mutation, the mutant produces 94% 12-hydroperoxyicosatetraenoate and 6% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 15% 12-hydroperoxyicosatetraenoate and 85% 15-hydroperoxyicosatetraenoate
L397M
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ratio of 15-lipoxygenation to 12-lipoxygenation is 9:1 for the wild-type enzyme and the mutant enzymes V104I, L397M and Q431R
L397M/M418V
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the ratio of 15-lipoxygenation to 12-lipoxygenation is 1:1 for the mutant enzymes V104/L397M/M418V/Q431R, L397M/M418V/Q431R, L397M/M418V and M418V, compared to 9:1 for the wild-type enzyme
L397M/M418V/Q431R
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the ratio of 15-lipoxygenation to 12-lipoxygenation is 1:1 for the mutant enzymes V104/L397M/M418V/Q431R, L397M/M418V/Q431R, L397M/M418V and M418V, compared to 9:1 for the wild-type enzyme
M418V
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the ratio of 15-lipoxygenation to 12-lipoxygenation is 1:1 for the mutant enzymes V104/L397M/M418V/Q431R, L397M/M418V/Q431R, L397M/M418V and M418V, compared to 9:1 for the wild-type enzyme
M419T
naturally occuring mutation, the mutant produces more 12-hydroperoxyicosatetraenoate compared to 15-hydroperoxyicosatetraenoate, incontrast to the wild-type, inversed substrate specificity
N287D
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relative catalytic activity: 1.1% compared to wild-type 100%
N287L
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relative catalytic activity: 0.5% compared to wild-type 100%
N287Q
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relative catalytic activity: 3.9% compared to wild-type 100%
Q294L
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relative catalytic activity: 0.6% compared to wild-type 100%
Q431R
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ratio of 15-lipoxygenation to 12-lipoxygenation is 9:1 for the wild-type enzyme and the mutant enzymes V104I, L397M and Q431R
T560A
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mutant shows strongly impaired catalytic activity, relative catalytic activity: 16.6% compared to wild-type 100%
T560S
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enzyme retains activity, relative catalytic activity: 70.7% compared to wild-type 100%
T594V
naturally occuring mutation, the mutant produces more 12-hydroperoxyicosatetraenoate compared to 15-hydroperoxyicosatetraenoate, incontrast to the wild-type, inversed substrate specificity
V104/L397M/M418V/Q431R
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the ratio of 15-lipoxygenation to 12-lipoxygenation is 1:1 for the mutant enzymes V104/L397M/M418V/Q431R, L397M/M418V/Q431R, L397M/M418V and M418V, compared to 9:1 for the wild-type enzyme
V104I
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ratio of 15-lipoxygenation to 12-lipoxygenation is 9:1 for the wild-type enzyme and the mutant enzymes V104I, L397M and Q431R
V603H
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a strong shift of the pH profile of 15-LOX-2 mutant towards more acidic values. 15-H(p)ETE is the major oxygenation product at pH 8
I418A
naturally occuring mutation, the mutant produces exclusively 12-hydroperoxyicosatetraenoate and almost no 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about equal amounts of both
I418F
naturally occuring mutation, the mutant produces more 15-hydroperoxyicosatetraenoate compared to 12-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about equal amounts of both
F353L
the ratio of turnover-number to KM-value is 4fold lower than the value for the wild-type enzyme. The mutation strongly alters the positional specificity of the oxygenation of most substrates in favor of 12-lipoxygenation except from (16(S),5Z,8Z,11Z,14Z)-16-hydroxyeicosa-5,8,11,14-tetraenoic acid
F412E
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mutation slightly impairs membrane binding, mutant enzyme shows 29% of the arachidonic acid oxygenase activity of the wild-type enzyme
F70H
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mutation impairs membrane binding, mutant enzyme shows 53% of the arachidonic acid oxygenase activity of the wild-type enzyme
I418A
naturally occuring mutation, the mutant produces 92% 12-hydroperoxyicosatetraenoate and 8% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
I593A
mutation induces alterations in the stereochemical characteristics of hydroxy fatty acid oxygenation
L195E
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mutation impairs membrane binding, mutant enzyme shows 42% of the arachidonic acid oxygenase activity of the wild-type enzyme
L367E
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367F
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, in silico mutagenesis and structural modeling, L367 is involved in oxygen access, overview
L367K
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367W
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L597A
site-directed mutagenesis, regiospecificity favoring addition to C15 is sharper than that in the wild-type, but the stereochemistry is R. This is because the extra space created by the mutation to Ala is big enough for arachidonate to move so that it can adopt an alternative binding mode. The L597A mutant of 15r-LO works as an aspirin-acetylated cyclooxygenase-2, which synthesizes 15-(R)-hydroperoxyeicosatetraenoic acid
L597V
site-directed mutagenesis, the addition of O2 to C15 of arachidonate is the predominant path, although it reduces the C15/C11 product ratio by almost ten times with respect to the wild-type enzyme. The S stereochemistry is kept
L71K
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mutation impairs membrane binding, mutant enzyme shows 50% of the arachidonic acid oxygenase activity of the wild-type enzyme
Q548L
site-directed mutagenesis, the mutation disrupts the hydrogen bond network inducing a loss in catalytic activity suggesting that this mutation might alter the structure of the iron cluster
W181E
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mutation strongly impairs membrane binding, mutant enzyme shows 34% of the arachidonic acid oxygenase activity of the wild-type enzyme
Y15E
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mutation impairs membrane binding, mutant enzyme shows 61% of the arachidonic acid oxygenase activity of the wild-type enzyme
Y292E
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mutation slightly impairs membrane binding, mutant enzyme shows 112% of the arachidonic acid oxygenase activity of the wild-type enzyme
I419A
H2QBX9
naturally occuring mutation, the mutant produces exclusively 12-hydroperoxyicosatetraenoate and almost no 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about 80% 15-hydroperoxyicosatetraenoate
I417A
naturally occuring mutation, the mutant produces 82% 12-hydroperoxyicosatetraenoate and 18% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 14% 12-hydroperoxyicosatetraenoate and 86% 15-hydroperoxyicosatetraenoate
T560M
naturally occurring enzyme mutant, the mutant shows 20fold reduced catalytic activity, genotyping using 12974 samples, the haplotypes show increased risk of coronary artery disease compared to non-carriers, overview
T560M
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mutant shows strongly impaired catalytic activity, relative catalytic activity: 3.8% compared to wild-type 100%
additional information
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endothelial 15-lipoxygenase-1 overexpression in Oryctolagus cuniculus aortic endothelial cells increases acetylcholine-induced hypotension and vasorelaxation, overview
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
additional information
generation of Alox15-deficient (12/15-LOX KO) mice
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
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additional information
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generation of Alox15-deficient (12/15-LOX KO) mice
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