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Literature summary extracted from

  • Augustin, P.; Hromic, A.; Pavkov-Keller, T.; Gruber, K.; Macheroux, P.
    Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant (2016), FEBS J., 283, 3587-3603 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.5.8.4 development of an intracellular, heterologous expression system in Komagataella phaffii (formerly known as Pichia pastoris). Initial attempts to express the gene in Escherichia coli (BL21 DE3) yielded largely insoluble protein. The H109R variant is expressed in lower amounts compared to the wild-type enzyme Homo sapiens
1.5.8.4 expressed in Komagataella phaffii KM71H cells Homo sapiens
1.5.8.4 expression in Komagataella phaffii, i.e. Pichia pastoris Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.8.4 crystallization of the wild-type enzyme and determination of the structure to 3.1A resolution, microbatch method using different commercial crystallization screens Homo sapiens
1.5.8.4 microbatch method using 10% (w/v) PEG 20000 and 20% (v/v) PEG MME 550 Homo sapiens
1.5.8.4 wild-type, to 3.1 resolution Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.5.8.4 H109R rare natural variant, suffers from decreased protein stability, cofactor saturation, and substrate affinity and causes dimethylglycine dehydrogenase deficiency leading to increased blood and urinary dimethylglycine concentrations Homo sapiens
1.5.8.4 H109R the mutation causes dimethylglycine dehydrogenase deficiency leading to increased blood and urinary dimethylglycine concentrations Homo sapiens
1.5.8.4 H109R rare natural variant, mutation leads to decreased protein stability, cofactor saturation, and substrate affinity Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.5.8.4 0.3
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, wild-type enzyme Homo sapiens
1.5.8.4 0.3
-
 N,N-dimethylglycine wild type enzyme, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 0.3
-
 oxidized 2,6-dichlorophenolindophenol wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 1.4
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, wild-type enzyme Homo sapiens
1.5.8.4 1.4
-
 N,N-dimethylglycine wild type enzyme, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 1.4
-
 Ferrocene wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 4.7
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, mutant enzyme H109R Homo sapiens
1.5.8.4 4.7
-
 N,N-dimethylglycine mutant enzyme H109R, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 4.7
-
 oxidized 2,6-dichlorophenolindophenol mutant H109R, pH 7.8, 25°C Homo sapiens
1.5.8.4 32.2
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, mutant enzyme H109R Homo sapiens
1.5.8.4 32.2
-
 N,N-dimethylglycine mutant enzyme H109R, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 32.2
-
 Ferrocene mutant H109R, pH 7.8, 25°C Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.5.8.4 mitochondrial matrix
-
 Homo sapiens 5759
-
1.5.8.4 mitochondrion
-
 Homo sapiens 5739
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.8.4 N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + electron-transfer flavoprotein Homo sapiens the enzyme takes part in choline degradation, one-carbon metabolism and electron transfer to the respiratory chain sarcosine + 5,10-methylenetetrahydrofolate + reduced electron-transfer flavoprotein
-
 ?
1.5.8.4 N,N-dimethylglycine + FAD + H2O Homo sapiens
-
 sarcosine + formaldehyde + FADH2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.5.8.4 Homo sapiens Q9UI17
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.8.4
-
 Homo sapiens
1.5.8.4 Ni-Sepharose 6 column chromatography and MonoQ column chromatography Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.8.4 N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + electron-transfer flavoprotein the enzyme takes part in choline degradation, one-carbon metabolism and electron transfer to the respiratory chain Homo sapiens sarcosine + 5,10-methylenetetrahydrofolate + reduced electron-transfer flavoprotein
-
 ?
1.5.8.4 N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + electron-transfer flavoprotein ferrocene or 2,6-dichlorophenolindophenol are used as artificial electron acceptor Homo sapiens sarcosine + 5,10-methylenetetrahydrofolate + reduced electron-transfer flavoprotein
-
 ?
1.5.8.4 N,N-dimethylglycine + FAD + H2O
-
 Homo sapiens sarcosine + formaldehyde + FADH2
-
 ?
1.5.8.4 N,N-dimethylglycine + ferricenium + H2O
-
 Homo sapiens sarcosine + formaldehyde + ferrocene
-
 ?
1.5.8.4 N,N-dimethylglycine + H2O + ferrocene
-
 Homo sapiens sarcosine + formaldehyde + ?
-
 ?
1.5.8.4 N,N-dimethylglycine + H2O + oxidized 2,6-dichlorophenolindophenol
-
 Homo sapiens sarcosine + formaldehyde + reduced 2,6-dichlorophenolindophenol
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.5.8.4 DMGDH
-
 Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
1.5.8.4 47
-
 melting point of mutant enzyme H109R Homo sapiens
1.5.8.4 47
-
 melting point, mutant H109R Homo sapiens
1.5.8.4 52
-
 melting point of wild-type enzyme Homo sapiens
1.5.8.4 52
-
 melting temperature Homo sapiens
1.5.8.4 52
-
 melting point, wild-type Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.5.8.4 0.73
-
 N,N-dimethylglycine wild type enzyme, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 0.73
-
 oxidized 2,6-dichlorophenolindophenol wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 0.733
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, wild-type enzyme Homo sapiens
1.5.8.4 1.5
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, mutant enzyme H109R Homo sapiens
1.5.8.4 1.52
-
 N,N-dimethylglycine mutant enzyme H109R, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 1.52
-
 oxidized 2,6-dichlorophenolindophenol mutant H109R, pH 7.8, 25°C Homo sapiens
1.5.8.4 3.55
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, wild-type enzyme Homo sapiens
1.5.8.4 3.55
-
 N,N-dimethylglycine wild type enzyme, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 3.55
-
 Ferrocene wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 9.07
-
 N,N-dimethylglycine mutant enzyme H109R, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 9.07
-
 Ferrocene mutant H109R, pH 7.8, 25°C Homo sapiens
1.5.8.4 9.1
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, mutant enzyme H109R Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.8.4 FAD flavoprotein Homo sapiens
1.5.8.4 FAD
-
 Homo sapiens
1.5.8.4 FAD A280/A450 ratios of the highly pure protein fractions are between 14-16 and 20-25 for wild-type and mutant H109R, respectively. The redox potential for the reduction of FAD is -93 mV Homo sapiens
1.5.8.4 tetrahydrofolate
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.5.8.4 malfunction rare natural mutation H109R, causes dimethylglycine dehydrogenase deficiency leading to increased blood and urinary dimethylglycine concentrations Homo sapiens
1.5.8.4 metabolism the enzyme takes part in choline degradation, one-carbon metabolism and electron transfer to the respiratory chain Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.5.8.4 0.18
-
 N,N-dimethylglycine mutant enzyme H109R, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 0.18
-
 Ferrocene mutant H109R, pH 7.8, 25°C Homo sapiens
1.5.8.4 0.28
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, mutant enzyme H109R Homo sapiens
1.5.8.4 0.32
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, mutant enzyme H109R Homo sapiens
1.5.8.4 0.33
-
 N,N-dimethylglycine mutant enzyme H109R, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 0.33
-
 oxidized 2,6-dichlorophenolindophenol mutant H109R, pH 7.8, 25°C Homo sapiens
1.5.8.4 2.28
-
 N,N-dimethylglycine wild type enzyme, with ferrocene as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 2.28
-
 Ferrocene wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 2.43
-
 N,N-dimethylglycine wild type enzyme, with 2,6-dichlorophenolindophenol as cosubstrate, at 25°C and pH 7.8 in 50 mM HEPES/NaOH with 150 mM NaCl Homo sapiens
1.5.8.4 2.43
-
 oxidized 2,6-dichlorophenolindophenol wild-type, pH 7.8, 25°C Homo sapiens
1.5.8.4 2.44
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: 2,6-dichlorophenolindophenol, wild-type enzyme Homo sapiens
1.5.8.4 2.54
-
 N,N-dimethylglycine 25°C, pH 7.8, artificial electron acceptor: ferrocene, wild-type enzyme Homo sapiens