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T354S
LG-F-B5, no activity with 1,2,3,4-tetrahydro-1-phenylisoquinoline
W230I/T354S/W430R
LG-F-B7, the mutant enzyme accepts the bulky substrate 1,2,3,4-tetrahydro-1-phenylisoquinoline with a specific activity of 0.3 U/mg
W230I/T354S/W430R/M242R/Y365V
LG-J-B4, specific activity towards 1,2,3,4-tetrahydro-1-phenylisoquinoline is improved more than 2fold as compared to mutant enzyme W230I/T354S/W430R
W230I/W430R
LG-F-B6, mutations change the size and thus shape of the active site pocket so that 1,2,3,4-tetrahydro-1-phenylisoquinoline is accepted with notable activity
W230R/W430C
LG-F-G6, specific activity towards 1,2,3,4-tetrahydro-1-methylisoquinoline is improved 6fold by mutant enzyme W230R/W430C/C214L as compared to mutant enzyme W230R/W430C
W230R/W430C/C214L
LG-I-D11, specific activity towards 1,2,3,4-tetrahydro-1-methylisoquinoline is improved 6fold as compared to mutant enzyme W230R/W430C, it is also active with 1,2,3,4-tetrahydro-1-phenylisoquinoline. When deracemizing 1,2,3,4-tetrahydro-1-methylisoquinoline on a preparative scale, the MAO-N variant allows access to the (S)-enantiomer. It also shows good activity in the preparation of (S)-1,2,3,4-tetrahydro-1-ethylisoquinoline and (S)-1,2,3,4-tetrahydro-1-isopropylisoquinoline on a preparative scale
C374A
mutation of surface cysteine 374 to alanine alters substrate turnover and inactivation by cyclopropylamines
C397A
-
expressed protein catalytically inactive
C397H
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expressed protein catalytically inactive
D123A
-
2.4fold increase in Km-value for phenylethylamine, 3.3fold increase in IC50-value for clorgyline, 3.3fold increase in IC50-value for deprenyl
D132A
-
2.2fold increase in Km-value for serotonin,1.8fold increase in IC50-value for clorgyline, 3.9fold increase in IC50-value for deprenyl
I199A/Y326A
-
the mutant exhibits catalytic properties with 75fold increased amine Km but unaltered kcat values. The mutant shows inhibitor binding properties more similar to those of isoform MAO A than to isoform MAO B. Benzylamine is a poor substrate for the double mutant
I199F
-
the bulky Phe side chain impedes such conformational flexibility, reduces the space of the entrance cavity and interferes with the binding of MAO B-specific inhibitors
K296A
-
no activity with phenylethylamine
K305A
-
no detectable activity with serotonin
S209A
site-directed mutagenesis of the phosphorylation site. The MAO A S209A mutant exhibits similar catalytic properties to those of wild-type enzyme, its catalytic activity is reduced by 1.5-3.7fold compared to the wild-type MAO A
S209E
site-directed mutagenesis of the phosphorylation site. Compared with purified wild-type and S209A MAO A proteins, the S209G MAO A mutant shows 10fold reduced kcat values and 10fold increased Km values compared to the wild-type enzymesignificant differences in covalent flavin fluorescence yield, circular dichroism spectra and thermal stability
W388A
-
no activity with phenylethylamine
W397A
-
no detectable activity with serotonin
Y398F
-
3.5fold increase in Km-value for phenylethylamine, 7.9fold increase in IC50-value for clorgyline, 15.5fold increase in IC50-value for deprenyl
Y398S
-
no activity with phenylethylamine
Y407S
-
no detectable activity with serotonin
Y435H
kcat/KM for benzylamine is 120fold lower than wild-type value, kcat/KM for p-trifluoromethyl-benzylamine is 13fold lower than wild-type value, kcat/KM for p-nitrobenzylamine is 4.4fold lower than wild-type value, kcat/KM for phenylethylamine is 1037fold lower than wild-type value, kcat/KM for p-nitrophenylethylamine is 45.2 fold lower than wild-type value
Y435L
kcat/KM for benzylamine is 128fold lower than wild-type value, kcat/KM for p-trifluoromethyl-benzylamine is 58fold lower than wild-type value, kcat/KM for phenylethylamine is 15.2fold lower than wild-type value, kcat/KM for p-nitrophenylethylamine is 2.7fold lower than wild-type value
Y435S
-
no activity with phenylethylamine
Y435W
kcat/KM for benzylamine is 9524fold lower than wild-type value, kcat/KM for phenylethylamine is 13889fold lower than wild-type value, kcat/KM for p-nitrophenylethylamine is 23fold lower than wild-type value
Y444S
-
no detectable activity with serotonin
C406A
-
MAO-A, Km for serotonin and tyramine not altered
Y402A
-
decrease in activity not significant, decrease in the FAD incorporation
Y403A
-
the ratio of turnover number to Km-value for serotonin is 95.6fold lower than that of the mutant enzyme, the ratio of turnover number to Km-value for phenylethylamine is 210fold lower than that of the wild-type enzyme, the ratio of turnover number to Km-value for tyramine is 170fold lower than that of the wild-type enzyme, the ratio of turnover number to KM-value for tryptamine is 91fold lower than that of the wild-type enzyme. Mutant enzyme is sensitive to trypsin treatment, while the wild-type enzyme is resistant
Y402A
-
decrease in activity not significant, decrease in the FAD incorporation
-
I199A
mutant of MAO-B, shows reduced inhibition by (E)-5-styrylisatin and (E)-6-styrylisatin compared to wild-type MAO-B
I199A
-
the mutant exhibits catalytic properties with 4fold increased amine Km but unaltered kcat values
Y407F
-
Km for kynuramine not altered, higher Km for benzylamine analogue
Y407F
-
1.4fold increase in Km-value for serotonin, 1.9fold increase in IC50-value for clorgyline, 10.9fold increase in IC50-value for deprenyl
Y435F
-
9.6fold increase in Km-value for phenylethylamine, 8.6fold increase in IC50-value for clorgyline, 130fold increase in IC50-value for deprenyl
Y435F
kcat/KM for benzylamine is 21.3fold lower than wild-type value, kcat/KM for p-trifluoromethyl-benzylamine is 40fold lower than wild-type value, kcat/KM for p-nitrobenzylamine is 4.1fold lower than wild-type value, kcat/KM for phenylethylamine is 35.9fold lower than wild-type value, kcat/KM for p-nitrophenylethylamine is 8.3fold lower than wild-type value
Y444F
-
mutation alters the substrate specificity, that depends on the size of the aromatic ring and on the length of the alkyl side chain of various substrate analogues
Y444F
-
activity with serotonin is too low to determine Km-value, 15.8fold increase in IC50-value for clorgyline, 10.4fold increase in IC50-value for deprenyl
Y402F
-
decrease in activity not significant
Y402F
-
the ratio of turnover number to Km-value for serotonin is 3.4fold lower than that of the mutant enzyme, the ratio of turnover number to Km-value for phenylethylamine is 3.3fold lower than that of the wild-type enzyme, the ratio of turnover number to Km-value for tyramine is 2.1fold lower than that of the wild-type enzyme, the ratio of turnover number to KM-value for tryptamine is 2.1fold lower than that of the wild-type enzyme
Y407A
-
no activity with serotonin, phenylethylamine, tyramine, low activity with tryptamine, decrease in the FAD incorporation
Y407A
-
mutation leads to almost complete loss of catalytic activity for serotonin, phenylethylamine, tyramine and tryptamine. Mutant enzyme is sensitive to trypsin treatment, while the wild-type enzyme is resistant
Y407F
-
little changes in Km for all substrates
Y407F
-
the ratio of turnover number to Km-value for serotonin is 2.6fold lower than that of the mutant enzyme, the ratio of turnover number to Km-value for phenylethylamine is 4.3fold lower than that of the wild-type enzyme, the ratio of turnover number to Km-value for tyramine is 2.7fold lower than that of the wild-type enzyme, the ratio of turnover number to KM-value for tryptamine is 1.3fold lower than that of the wild-type enzyme
Y410A
-
decrease in activity not significant
Y410A
-
the ratio of turnover number to Km-value for serotonin is 7.8fold lower than that of the mutant enzyme, the ratio of turnover number to Km-value for phenylethylamine is 6fold lower than that of the wild-type enzyme, the ratio of turnover number to Km-value for tyramine is 3.4fold lower than that of the wild-type enzyme, the ratio of turnover number to KM-value for tryptamine is 3.4fold lower than that of the wild-type enzyme. Mutant enzyme is sensitive to trypsin treatment, while the wild-type enzyme is resistant
Y407A
-
no activity with serotonin, phenylethylamine, tyramine, low activity with tryptamine, decrease in the FAD incorporation
-
Y407A
-
mutation leads to almost complete loss of catalytic activity for serotonin, phenylethylamine, tyramine and tryptamine. Mutant enzyme is sensitive to trypsin treatment, while the wild-type enzyme is resistant
-
Y407F
-
little changes in Km for all substrates
-
Y407F
-
the ratio of turnover number to Km-value for serotonin is 2.6fold lower than that of the mutant enzyme, the ratio of turnover number to Km-value for phenylethylamine is 4.3fold lower than that of the wild-type enzyme, the ratio of turnover number to Km-value for tyramine is 2.7fold lower than that of the wild-type enzyme, the ratio of turnover number to KM-value for tryptamine is 1.3fold lower than that of the wild-type enzyme
-
additional information
the variant D9 exhibits the highest activity for most substrates and is applied to the deracemisation of a comprehensive set of selected primary amines. In all cases, excellent enantioselectivity is achieved (enantiomeric excess is higher than 99%) with moderate to good yields (55-80%)
additional information
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MAO-A chimeric form containing the N-terminus of MAO-B, the first 36 acid sequence, do not significantly differ in their affinity for 5-hydroxytryptamine and phenylethylamine, MAO-B chimeric form containing the N-terminus of MAO-A , the first 45 acid sequence, but kinetic properties could not be detemined
additional information
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determination of single nucleotide polymorphisms in the MAOA gene, the most frequent haplotype AGG contains rs5906883, rs1137070, and rs3027407 in autism spectrum disorder, ASD
additional information
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construction of transgenic mice lacking monoamine oxidase A. The mice exhibit about 3fold higher rates of central sleep apnea than wild-types, linked to enhanced 5-hydroxytryptamine levels. Acute ondansetron and fluoxetine, and 13-day chronic fluoxetine decreas by 80% the total apnea index in the mutant mice during non-rapid eye movement sleep, with no statistically significant effect on apnea in C3H mice. Our study shows that both drugs reduce the frequency of apneic episodes attributable to increased monoamine levels in this model of MAOA deficiency, phenotypes, detailed overview