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Literature summary for 2.5.1.6 extracted from

  • Huber, T.D.; Clinger, J.A.; Liu, Y.; Xu, W.; Miller, M.D.; Phillips, G.N.; Thorson, J.S.
    Methionine adenosyltransferase engineering to enable bioorthogonal platforms for AdoMet-utilizing enzymes (2020), ACS Chem. Biol., 15, 695-705 .
    View publication on PubMed
Search for more literature for 2.5.1.6

Protein Variants

Protein Variants Comment Organism
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) Homo sapiens
K289F the mutant enzyme lacks selectivity (33% (3S)-3-amino-5-(methylthio)pentan-2-ol versus 30% L-Met, 240 min) Homo sapiens
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 Homo sapiens
K289S mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (38%, 240 min) over L-Met (14%, 240 min) Homo sapiens
K289T mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (14%, 240 min) over L-Met (2.5%, 240 min) Homo sapiens
Q113D mutant displays selectivity toward (3S)-3-amino-5-(methylthio)pentan-2-ol (39%, 240 min) over L-Met (13%, 240 min) Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.047
-
 L-methionine pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
0.078
-
 L-methionine pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
0.14
-
 L-methionine pH 8.0, 37°C, wild-type enzyme Homo sapiens
0.39
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
1
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
2.4
-
 S-(-)-methioninol pH 8.0, 37°C, wild-type enzyme Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-methionine + H2O Homo sapiens
-
 phosphate + diphosphate + S-adenosyl-L-methionine
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P31153
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + (3S)-3-amino-5-(methylthio)pentan-2-ol + H2O
-
 Homo sapiens phosphate + diphosphate + ?
-
 ?
ATP + L-methionine + H2O
-
 Homo sapiens phosphate + diphosphate + S-adenosyl-L-methionine
-
 ?
ATP + S-(-)-methioninol + H2O
-
 Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
methionine adenosyltransferase II-alpha
-
 Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.013
-
 L-methionine pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
0.02
-
 L-methionine pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
0.055
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
0.068
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
0.183
-
 S-(-)-methioninol pH 8.0, 37°C, wild-type enzyme Homo sapiens
0.43
-
 L-methionine pH 8.0, 37°C, wild-type enzyme Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.076
-
 S-(-)-methioninol pH 8.0, 37°C, wild-type enzyme Homo sapiens
0.141
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
0.167
-
 L-methionine pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
0.43
-
 L-methionine pH 8.0, 37°C, mutant enzyme Q113D Homo sapiens
0.68
-
 S-(-)-methioninol pH 8.0, 37°C, mutant enzyme K289L Homo sapiens
3.07
-
 L-methionine pH 8.0, 37°C, wild-type enzyme Homo sapiens