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2.5.1.6: methionine adenosyltransferase

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

Word Map on EC 2.5.1.6

Reaction

ATP
+
L-methionine
 +
H2O
=
phosphate
 +
diphosphate
 +
S-adenosyl-L-methionine

Synonyms

(Met) adenosyltransferase 4, adenosylmethionine synthase, adenosylmethionine synthetase, AdoMet synthase, AdoMet synthease, AdoMet synthetase, AdoMetS, ATP-methionine adenosyltransferase, ATP: L-methionine S-adenosyltransferase, EC 2.4.2.13, MAT, MAT I, MAT II, MAT IIalpha, MAT III, MAT1A, MAT2, MAT2A, MAT2beta, MAT3, MAT4, MATalpha1, MATalpha2, methionine adenosyl transferase 2A, methionine adenosyltransferase, methionine adenosyltransferase 2A, methionine adenosyltransferase 2beta, methionine adenosyltransferase 4, methionine adenosyltransferase alpha1, methionine adenosyltransferase II, methionine adenosyltransferase II-alpha, methionine adenosyltransferase IIalpha, methionine S-adenosyltransferase, methionine-activating enzyme, MetK, Mj-MAT, MJ1208, pDS16, PF1866, PfMAT, S-adenosyl-L-methionine synthetase, S-adenosyl-Lmethionine synthetase, S-adenosyl-Met synthetase 3, S-adenosylmethionine synthase, S-adenosylmethionine synthetase, S-adenosylmethionine synthetase 1, S-adenosylmethionine synthetase 2, S-adenosylmethionine synthetase 3, S-adenosylmethionine synthetase A, S-adenosylmethionine synthetase B, S-adenosylmethionine-L-synthetase, SAM synthase, SAM synthetase, SAM-s, Sam1, SAM2, SAMS, SAMS1, SAMS2, SMAT, SSO0199

ECTree

     2 Transferases
         2.5 Transferring alkyl or aryl groups, other than methyl groups
             2.5.1 Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)
                2.5.1.6 methionine adenosyltransferase

Engineering

Engineering on EC 2.5.1.6 - methionine adenosyltransferase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I105A/I317A
-
the conversion of the natural substrate methionine is reduced in this mutant
I105V/I317A
-
the conversion of the natural substrate methionine is reduced in this mutant
I105A/I317A
-
the conversion of the natural substrate methionine is reduced in this mutant
-
I105V/I317A
-
the conversion of the natural substrate methionine is reduced in this mutant
-
H145Y
spontaneous mutant, excretes a large amount of a red compound identified as coproporphyrin III. The mutant is able to grow under phototrophic conditions but has low levels of intracellular cysteine and glutathione and overexpresses the cysteine synthase CysK. The wild-type phenotype is restored when the gene metK encoding SAM synthetase is supplied in trans. The mutation is responsible for a 70% decrease in intracellular SAM content which probably affects the activities of numerous SAM-dependent enzymes such as coproporphyrinogen oxidase, uroporphyrinogen III methyltransferase, and molybdenum cofactor biosynthesis protein A
D107C
enzyme activity similar to wild-type, attachment of methanethiosulfonate spin label to form D107R1, increase in Km-value, decrease in kcat value
G105C
enzyme activity similar to wild-type, attachment of methanethiosulfonate spin label to form G105R1, increase in Km-value
I303V
-
the Km-values for both substrates are slightly less than those of the wild-type enzyme. The variant is successfully produced at a high level (about 800 mg/l) with approximately four-fold higher specific activity than the wild-type enzyme. The recombinant mutant enzyme is covalently immobilized onto the amino resin and epoxy resin in order to obtain a robust biocatalyst to be used in industrial bioreactors. The immobilized preparation using amino resin exhibits the highest activity coupling yield (about 84%), compared with approximately 3% for epoxy resin. The immobilized mutant enzyme is more stable than the soluble enzyme under the reactive conditions, with a half-life of 229.5 h at 37 °C. The Km(ATP) value (0.18 mM) of the immobilized mutant enzyme is about two-fold lower than that of the soluble enzyme. The immobilized enzyme shows high operational stability during 10 consecutive 8 h batches, with the substrate adenosine triphosphate conversion rate above 95% on the 50 mM scale. Compared with the wild-type enzyme, as little as 200 mM sodium p-toluenesulfonate is required to completely overcome the product inhibition by S-adenosyl-L-methionine of I303V mutant enzyme on a 30 mM scale incubation
I303V/I65V/L186V
product inhibition of the enzyme is reduced via semi-rational modification. The mutant enzyme shows a 42fold increase in Ki(ATP) and a 2.08fold increase in specific activity when compared to wild-type enzyme. Its Ki(ATP) is 0.42 mM and specific acitivity is 3.78 U/mg. Increased Ki(ATP) means reduced product inhibition which enhances accumulation of S-adenosyl-L-methionine. The S-adenosyl-L-methionine produced by the variant could reach to 3.27 mM while S-adenosyl-L-methionine produced by wild-type enzyme is 1.62 mM in the presence of 10 mM substrates
I303V/I65V/L186V/N104K
product inhibition of the enzyme is reduced via semi-rational modification. The mutant enzyme shows a 3.3fold increase in specific activity when compared to wild-type enzyme. Specific acitivity of the mutant enzyme is 6.02 U/mg. Increased Ki(ATP) means reduced product inhibition which enhances accumulation of S-adenosyl-L-methionine. The S-adenosyl-L-methionine produced by the variant could reach to 2.68 mM while S-adenosyl-L-methionine produced by wild-type enzyme is 1.62 mM in the presence of 10 mM substrates
I303V
-
the Km-values for both substrates are slightly less than those of the wild-type enzyme. The variant is successfully produced at a high level (about 800 mg/l) with approximately four-fold higher specific activity than the wild-type enzyme. The recombinant mutant enzyme is covalently immobilized onto the amino resin and epoxy resin in order to obtain a robust biocatalyst to be used in industrial bioreactors. The immobilized preparation using amino resin exhibits the highest activity coupling yield (about 84%), compared with approximately 3% for epoxy resin. The immobilized mutant enzyme is more stable than the soluble enzyme under the reactive conditions, with a half-life of 229.5 h at 37 °C. The Km(ATP) value (0.18 mM) of the immobilized mutant enzyme is about two-fold lower than that of the soluble enzyme. The immobilized enzyme shows high operational stability during 10 consecutive 8 h batches, with the substrate adenosine triphosphate conversion rate above 95% on the 50 mM scale. Compared with the wild-type enzyme, as little as 200 mM sodium p-toluenesulfonate is required to completely overcome the product inhibition by S-adenosyl-L-methionine of I303V mutant enzyme on a 30 mM scale incubation
-
I303V/I65V/L186V
-
product inhibition of the enzyme is reduced via semi-rational modification. The mutant enzyme shows a 42fold increase in Ki(ATP) and a 2.08fold increase in specific activity when compared to wild-type enzyme. Its Ki(ATP) is 0.42 mM and specific acitivity is 3.78 U/mg. Increased Ki(ATP) means reduced product inhibition which enhances accumulation of S-adenosyl-L-methionine. The S-adenosyl-L-methionine produced by the variant could reach to 3.27 mM while S-adenosyl-L-methionine produced by wild-type enzyme is 1.62 mM in the presence of 10 mM substrates
-
I303V/I65V/L186V/N104K
-
product inhibition of the enzyme is reduced via semi-rational modification. The mutant enzyme shows a 3.3fold increase in specific activity when compared to wild-type enzyme. Specific acitivity of the mutant enzyme is 6.02 U/mg. Increased Ki(ATP) means reduced product inhibition which enhances accumulation of S-adenosyl-L-methionine. The S-adenosyl-L-methionine produced by the variant could reach to 2.68 mM while S-adenosyl-L-methionine produced by wild-type enzyme is 1.62 mM in the presence of 10 mM substrates
-
A55D
the mutation reduces the enzyme activity by more than 50%
D258G
the mutation reduces the enzyme activity by more than 50%
E70S
the mutant enzyme lacks appreciable activity in the presence of non-native methionine surrogates (3.2% S-(-)-methioninol, 240 min versus 25% L-Met, 20 min)
I322M
the mutation reduces the enzyme activity by more than 50%
K289F
the mutant enzyme lacks selectivity (33% (3S)-3-amino-5-(methylthio)pentan-2-ol versus 30% L-Met, 240 min)
K289L
160fold inversion of the enzyme (hMAT2A) selectivity index for a non-native methionine analogue over the native substrate L-methionine. Structure elucidation of K289L reveales the mutant to be folded normally with minor observed repacking within the modified substrate pocket. It is an example of exchanging L-Met terminal carboxylate/amine recognition elements within the hMAT2A active-site to enable non-native bioorthgonal substrate utilization
K289S
mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (38%, 240 min) over L-Met (14%, 240 min)
K289T
mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (14%, 240 min) over L-Met (2.5%, 240 min)
Q113D
mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (39%, 240 min) over L-Met (13%, 240 min)
R264H
the mutation almost completely abolishes enzyme activity
D121N
no basal enzymic activity, little activity in presence of S-adenosyl methionine
D166N
reduced enzymic activity, little activation by S-adenosyl methionine
D19N
no basal enzymic activity, little activity in presence of S-adenosyl methionine
D249N
reduced enzymic activity, little activation by S-adenosyl methionine
D277N
no enzymic activity
D282N
reduced enzymic activity, little activation by S-adenosyl methionine
F241A
no enzymic activity, but hydrolysis of triphosphate
H17A
no basal enzymic activity, little activity in presence of S-adenosyl methionine
H17N
no basal enzymic activity, little activity in presence of S-adenosyl methionine
K168A
no enzymic activity
K256A
no activation by S-adenosyl methionine
K276A
no enzymic activity
K280A
enhanced enzymic activity, little activation by S-adenosyl methionine
R255L
no enzymic activity
W387F
W387F/Y120W
W387F/Y170W
W387F/Y226W
W387F/Y233W
W387F/Y255W
W387F/Y267W
W387F/Y273W
W387F/Y323W
W387F/Y344W
W387F/Y371W
W387F/Y49W
W387F/Y72W
W387F/Y85W
W387F
-
the mutant is active and dimeric, and shows no dramatic alterations in its affinity for the substrates or far-UV CD spectra due to mutations. Unfolding of the wild-type enzyme in guanidinium chloride is a three-state process in which a dimeric intermediate can be identified. The mutant enzyme exhibits two inactivation transitions in guanidinium chloride
-
W387F/Y120W
-
the mutant is active and dimeric, and shows no dramatic alterations in its affinity for the substrates or far-UV CD spectra due to mutations. Lower resistance to guanidinium chloride than the wild type enzyme
-
W387F/Y49W
-
the mutant is active and dimeric, and shows no dramatic alterations in its affinity for the substrates or far-UV CD spectra due to mutations. Unfolding of the wild-type enzyme in guanidinium chloride is a three-state process in which a dimeric intermediate can be identified. The mutant enzyme shows a single inactivation transition
-
W387F/Y72W
-
the mutant is active and dimeric, and shows no dramatic alterations in its affinity for the substrates or far-UV CD spectra due to mutations. Unfolding of the wild-type enzyme and mutant enzyme W387F/Y72W in guanidinium chloride is a three-state process. Lower resistance to guanidinium chloride than the wild type enzyme
-
W387F/Y85W
-
the mutant is active and dimeric, and shows no dramatic alterations in its affinity for the substrates or far-UV CD spectra due to mutations. Unfolding of the wild-type enzyme in guanidinium chloride is a three-state process in which a dimeric intermediate can be identified. The mutant enzyme exhibits two inactivation transitions in guanidinium chloride
-
C113S
compared with the wild type enzyme the mutant enzyme is only weakly activated by PfTrx1. The mutation significantly decreases the affinity to the substrate L-methionine. The mutant enzyme shows higher affinity towards ATP when compared with the wild type
C187S
with regard to specific activity the mutant enzyme does not show major differences compared with the wild type enzyme. The mutant enzyme shows higher affinity towards ATP when compared with the wild type
C52S
compared with the wild type enzyme the mutant enzyme is only weakly activated by PfTrx1. With regard to specific activity the mutant enzyme does not show major differences compared with the wild type enzyme. The mutation significantly decreases the affinity to the substrate L-methionine and ATP
C35S
reduction in Vmax value
C61S
reduction in Vmax value
F251D
-
inactive, but displays correct nuclear localization and matrix binding
additional information