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Synonyms
pfmdh, mannitol 2-dehydrogenase, mannitol-2-dehydrogenase, nadh-dependent mannitol dehydrogenase, nad+-dependent mannitol dehydrogenase, psm2dh, tm0298,
more
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D-mannitol + NAD+ = D-fructose + NADH + H+
D-mannitol + NAD+ = D-fructose + NADH + H+

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D-mannitol + NAD+ = D-fructose + NADH + H+
the oxyanion hole of mannitol 2-dehydrogenase drives a precatalytic conformational equilibrium at the ternary complex level in which the reactive group of the substrate is activated for chemical conversion through its precise alignment with the unprotonated side chain of Lys295 in mannitol oxidation and C=O bond polarization by the carboxamide moieties of Asn191 and Asn300 in fructose reduction. In the subsequent hydride transfer step, the two asparagine residues provide about 40 kJ/mol of electrostatic stabilization
D-mannitol + NAD+ = D-fructose + NADH + H+
binding of substrate and NAD(H) is random for both D-mannitol oxidation and D-fructose reduction. Hydride transfer is rate-determining for D-fructose reduction. Product release steps control the maximum rates in the other direction of the enzymatic reaction
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arabitol + NAD(P)+
? + NAD(P)H
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?
D-arabinitol + NAD+
D-ribulose + NADH + H+
D-arabinitol + NAD+
D-xylulose + NADH + H+
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r
D-arabitol + NAD+
?
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?
D-arabitol + NAD+
? + NADH
D-fructose + NAD(P)+
? + NAD(P)H
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?
D-fructose + NADH + H+
D-mannitol + NAD+
D-fructose + NADPH + H+
D-mannitol + NADP+
D-fructose + polyethylenimine-NH-succinyl-NADH + H+
D-mannitol + polyethylenimine-NH-succinyl-NAD+
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r
D-fructose 1-phosphate + NADH
?
D-glucitol + NAD+
?
4% of the activity with D-mannitol
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?
D-glucitol + NAD+
? + NADH
D-mannitol + NAD(P)+
D-fructose + NAD(P)H + H+
D-mannitol + NAD+
D-fructose + NADH + H+
D-mannitol + NADP+
D-fructose + NADPH + H+
D-mannitol + polyethyleneglycol-NH-succinyl-aminoethyl-NAD+
D-fructose + polyethyleneglycol-NH-succinyl-aminoethyl-NADH
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?
D-mannitol + polyethyleneglycol-NH-succinyl-NAD+
D-fructose + polyethyleneglycol-NH-succinyl-NADH
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?
D-mannitol + polyethylenimin-NH-succinyl-NAD+
D-fructose + polyethylenimin-NH-succinyl-NADH
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?
D-sorbitol + NAD+
?
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r
D-tagatose + NAD(P)+
? + NAD(P)H
29% relative activity compared to D-fructose
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?
D-tagatose + NAD+
?
29% relative activity on D-tagatose compared to 100% activity on D-fructose
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?
D-xylose + NADH + H+
D-xylitol + NAD+
18% activity compared to D-fructose
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r
D-xylulose + NAD(P)+
? + NAD(P)H
18% relative activity compared to D-fructose
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?
D-xylulose + NAD+
?
18% relative activity on D-xylulose compared to 100% activity on D-fructose
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?
D-xylulose + NADH + H+
D-arabinitol + NAD+
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?
isomaltulose + NAD(P)+
? + NAD(P)H
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?
L-sorbitol + NAD+
L-sorbose + NADH + H+
L-sorbose + NAD(P)+
? + NAD(P)H
5% relative activity compared to D-fructose
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?
L-sorbose + NADH + H+
L-sorbitol + NAD+
meso-erythritol + NAD+
?
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?
sorbitol + NAD(P)+
? + NAD(P)H
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?
targatose + NADH + H+
? + NAD+
29% activity compared to D-fructose
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r
additional information
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D-arabinitol + NAD+

D-ribulose + NADH + H+
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?
D-arabinitol + NAD+
D-ribulose + NADH + H+
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?
D-arabinitol + NAD+
D-ribulose + NADH + H+
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?
D-arabinitol + NAD+
D-ribulose + NADH + H+
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?
D-arabitol + NAD+

? + NADH
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?
D-arabitol + NAD+
? + NADH
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?
D-fructose + NADH + H+

D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
-mannitol production
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
-mannitol production
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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Asn300 has an auxiliary role in stabilization of the transition state of hydride transfer and His303 contributes to substrate positioning, role of Lys295 in general base enzymic catalysis
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D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
the Thermotoga maritima MtDH pathway produces D-mannitol from glucose in two steps: first the xylose isomerase from Thermotoga neapolitana converts glucose to fructose, then MtDH converts D-fructose to D-mannitol
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
the Thermotoga maritima MtDH pathway produces D-mannitol from glucose in two steps: first the xylose isomerase from Thermotoga neapolitana converts glucose to fructose, then MtDH converts D-fructose to D-mannitol
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D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
the Thermotoga maritima MtDH pathway produces D-mannitol from glucose in two steps: first the xylose isomerase from Thermotoga neapolitana converts glucose to fructose, then MtDH converts D-fructose to D-mannitol
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D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
the Thermotoga maritima MtDH pathway produces D-mannitol from glucose in two steps: first the xylose isomerase from Thermotoga neapolitana converts glucose to fructose, then MtDH converts D-fructose to D-mannitol
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D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
the Thermotoga maritima MtDH pathway produces D-mannitol from glucose in two steps: first the xylose isomerase from Thermotoga neapolitana converts glucose to fructose, then MtDH converts D-fructose to D-mannitol
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADH + H+
D-mannitol + NAD+
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r
D-fructose + NADH + H+
D-mannitol + NAD+
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?
D-fructose + NADPH + H+

D-mannitol + NADP+
low activity
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r
D-fructose + NADPH + H+
D-mannitol + NADP+
also active on fructose with NADPH
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?
D-fructose + NADPH + H+
D-mannitol + NADP+
low activity
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r
D-fructose + NADPH + H+
D-mannitol + NADP+
low activity
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r
D-fructose + NADPH + H+
D-mannitol + NADP+
low activity
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r
D-fructose + NADPH + H+
D-mannitol + NADP+
also active on fructose with NADPH
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?
D-fructose + NADPH + H+
D-mannitol + NADP+
low activity
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r
D-fructose 1-phosphate + NADH

?
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?
D-fructose 1-phosphate + NADH
?
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?
D-glucitol + NAD+

? + NADH
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?
D-glucitol + NAD+
? + NADH
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?
D-mannitol + NAD(P)+

D-fructose + NAD(P)H + H+
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r
D-mannitol + NAD(P)+
D-fructose + NAD(P)H + H+
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r
D-mannitol + NAD(P)+
D-fructose + NAD(P)H + H+
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r
D-mannitol + NAD+

D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
free energy profiles for the enzymatic reaction suggest that enzyme primarily acts in D-mannitol oxidation
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?, r
D-mannitol + NAD+
D-fructose + NADH + H+
Fomes pinicola
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
Lactobacillus gayonii
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?
D-mannitol + NAD+
D-fructose + NADH + H+
Lactobacillus gayonii
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?
D-mannitol + NAD+
D-fructose + NADH + H+
Lactobacillus pentoaceticus
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?
D-mannitol + NAD+
D-fructose + NADH + H+
Lactobacillus pentoaceticus
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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-
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-
?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
-
-
?
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
-
?
D-mannitol + NAD+
D-fructose + NADH + H+
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-
-
-
?
D-mannitol + NAD+
D-fructose + NADH + H+
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-
?
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
enzyme highly specific for D-mannitol and D-fructose
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
enzyme highly specific for D-mannitol and D-fructose
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
Nocardia erythropolis
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
the epsilon-NH2 group of Lys295 participates in an obligatory pH-dependent, pre-catalytic equilibrium which may control alcohol/alkoxide equilibration of the enzyme-bound D-mannitol and activates the C2 atom for subsequent catalytic oxidation by NAD+
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D-mannitol + NAD+
D-fructose + NADH + H+
wild-type enzyme
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
Sarcina aurantiaca
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?
D-mannitol + NAD+
D-fructose + NADH + H+
Sarcina marginata
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
-
?
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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-
?
D-mannitol + NAD+
D-fructose + NADH + H+
-
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r
D-mannitol + NAD+
D-fructose + NADH + H+
100% activity
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r
D-mannitol + NAD+
D-fructose + NADH + H+
100% activity
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r
D-mannitol + NAD+
D-fructose + NADH + H+
-
-
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NAD+
D-fructose + NADH + H+
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?
D-mannitol + NAD+
D-fructose + NADH + H+
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r
D-mannitol + NADP+

D-fructose + NADPH + H+
M2DH is a much poorer enzyme when it employes NADP+ and NADPH as compared to NAD+ and NADH
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r
D-mannitol + NADP+
D-fructose + NADPH + H+
32% of the activity with NAD+
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?
L-sorbitol + NAD+

L-sorbose + NADH + H+
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r
L-sorbitol + NAD+
L-sorbose + NADH + H+
-
-
-
?
L-sorbitol + NAD+
L-sorbose + NADH + H+
-
-
-
?
L-sorbitol + NAD+
L-sorbose + NADH + H+
-
-
-
?
L-sorbitol + NAD+
L-sorbose + NADH + H+
-
-
-
?
L-sorbose + NADH + H+

L-sorbitol + NAD+
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r
L-sorbose + NADH + H+
L-sorbitol + NAD+
5% relative activity on L-sorbose compared to 100% activity on D-fructose
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?
L-sorbose + NADH + H+
L-sorbitol + NAD+
5% activity compared to D-fructose
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r