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Literature summary for 1.1.1.17 extracted from

  • Krahulec, S.; Armao, G.C.; Klimacek, M.; Nidetzky, B.
    Enzymes of mannitol metabolism in the human pathogenic fungus Aspergillus fumigatus--kinetic properties of mannitol-1-phosphate 5-dehydrogenase and mannitol 2-dehydrogenase, and their physiological implications (2011), FEBS J., 278, 1264-1276.
    View publication on PubMed

Application

Application Comment Organism
pharmacology inhibition of AfM1PDH might be a useful target for therapy of Aspergillus fumigatus infections Aspergillus fumigatus

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression in Escherichia coli Aspergillus fumigatus

Inhibitors

Inhibitors Comment Organism Structure
additional information poor effects by ATP, ADP and AMP Aspergillus fumigatus
NADH
-
Aspergillus fumigatus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics and kinetic mechanism, binding of D-mannitol 1-phosphate and NAD+ is random, whereas D-fructose 6-phosphate binds only after NADH has bound to the enzyme. Hydride transfer is rate-determining for D-mannitol 1-phosphate oxidation by AfM1PDH. AfM1PDH behaves kinetically as a fructose 6-phosphate reductase, overview Aspergillus fumigatus
0.014
-
NADH pH 10.0, 25°C, recombinant enzyme Aspergillus fumigatus
0.13
-
D-mannitol 1-phosphate pH 7.1, 25°C, recombinant enzyme Aspergillus fumigatus
0.8
-
NAD+ pH 7.1, 25°C, recombinant enzyme Aspergillus fumigatus
3.2
-
D-fructose 6-phosphate pH 10.0, 25°C, recombinant enzyme Aspergillus fumigatus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-mannitol 1-phosphate + NAD+ Aspergillus fumigatus AfM1PDH primarily functions as a D-fructose-6-phosphate reductase and is specific for its natural pair of substrates D-fructose 6-phosphate + NADH + H+
-
r

Organism

Organism UniProt Comment Textmining
Aspergillus fumigatus
-
-
-

Reaction

Reaction Comment Organism Reaction ID
D-mannitol 1-phosphate + NAD+ = D-fructose 6-phosphate + NADH + H+ the phosphate moiety in Man-ol1P and Fru6P is essential for substrate recognition and/or catalysis by Aspergillus fumigatus M1PDH. Binding of D-mannitol 1-phosphate and NAD+ is random, whereas D-fructose 6-phosphate binds only after NADH has bound to the enzyme. Hydride transfer is rate-determining for D-mannitol 1-phosphate oxidation by AfM1PDH. The enzyme behaves kinetically as a fructose 6-phosphate reductase Aspergillus fumigatus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-mannitol 1-phosphate + NAD+ AfM1PDH primarily functions as a D-fructose-6-phosphate reductase and is specific for its natural pair of substrates Aspergillus fumigatus D-fructose 6-phosphate + NADH + H+
-
r
additional information M1PDH does not catalyze the oxidation of D-mannitol, D-sorbitol, D-ribitol, xylitol, D-xylose, L-xylose, D-glucose, D-mannose, L-arabinose, D-arabinose, D-galactose, L-fucose, and D-lyxose. The enzyme is also inactive above a level of 1% activity with D-fructose 6-phosphate for reduction of D-fructose, L-sorbose, D-xylulose, D-fructose 1,6-bisphosphate, D-glucose 6-phosphate, and D-glucose 1-phosphate Aspergillus fumigatus ?
-
?

Synonyms

Synonyms Comment Organism
M1PDH
-
Aspergillus fumigatus
NADH-dependent mannitol-1-phosphate 5-dehydrogenase
-
Aspergillus fumigatus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Aspergillus fumigatus

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
40 50 half-life is 20 h at 40°C, the enzyme displays remarkable stability at 40°C and even at 50°C Aspergillus fumigatus

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
10.6
-
D-mannitol 1-phosphate pH 7.1, 25°C, recombinant enzyme Aspergillus fumigatus
132
-
D-fructose 6-phosphate pH 10.0, 25°C, recombinant enzyme Aspergillus fumigatus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.1
-
assay at, reduction reaction Aspergillus fumigatus
10
-
assay at, oxidation reaction Aspergillus fumigatus

Cofactor

Cofactor Comment Organism Structure
additional information NADP+ is a poor cofactor substrate Aspergillus fumigatus
NAD+
-
Aspergillus fumigatus
NADH
-
Aspergillus fumigatus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.002
-
NADH pH 10.0, 25°C, recombinant enzyme Aspergillus fumigatus

Expression

Organism Comment Expression
Aspergillus fumigatus M1PDH becomes strongly upregulated during heat shock up

General Information

General Information Comment Organism
additional information ATP, ADP and AMP do not affect the activity of AfM1PDH, suggesting the absence of flux control by cellular energy charge at the level of D-fructose 6-phosphate reduction Aspergillus fumigatus
physiological function formation of mannitol is an essential component of the temperature stress response of Aspergillus fumigatus. Enhanced biosynthesis of d-mannitol via AfM1PDH-catalyzed conversion of fructose 6-phosphate might contribute extra robustness to Aspergillus fumigatus under high temperature conditions Aspergillus fumigatus

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
41
-
D-fructose 6-phosphate pH 10.0, 25°C, recombinant enzyme Aspergillus fumigatus
80
-
D-mannitol 1-phosphate pH 7.1, 25°C, recombinant enzyme Aspergillus fumigatus