The Enzyme Database

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EC 1.5.8.4     
Accepted name: dimethylglycine dehydrogenase
Reaction: N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + electron-transfer flavoprotein = sarcosine + 5,10-methylenetetrahydrofolate + reduced electron-transfer flavoprotein
Glossary: sarcosine = N-methylglycine
Other name(s): N,N-dimethylglycine oxidase; N,N-dimethylglycine:(acceptor) oxidoreductase (demethylating); Me2GlyDH; N,N-dimethylglycine:electron-transfer flavoprotein oxidoreductase (demethylating)
Systematic name: N,N-dimethylglycine,5,6,7,8-tetrahydrofolate:electron-transferflavoprotein oxidoreductase (demethylating,5,10-methylenetetrahydrofolate-forming)
Comments: A flavoprotein, containing a histidyl(Nπ)-(8α)FAD linkage at position 91 in the human protein. An imine intermediate is channeled from the FAD binding site to the 5,6,7,8-tetrahydrofolate binding site through a 40 Å tunnel [5,8,9]. In the absence of 5,6,7,8-tetrahydrofolate the enzyme forms formaldehyde [5,9].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-30-7
References:
1.  Frisell, W.R. and MacKenzie, C.G. Separation and purification of sarcosine dehydrogenase and dimethylglycine dehydrogenase. J. Biol. Chem. 237 (1962) 94–98. [PMID: 13895406]
2.  Hoskins, D.D. and MacKenzie, C.G. Solubilization and electron transfer flavoprotein requirement of mitochondrial sarcosine dehydrogenase and dimethylglycine dehydrogenase. J. Biol. Chem. 236 (1961) 177–183. [PMID: 13716069]
3.  Wittwer, A.J. and Wagner, C. Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Purification and folate-binding characteristics. J. Biol. Chem. 256 (1981) 4102–4108. [PMID: 6163777]
4.  Wittwer, A.J. and Wagner, C. Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Flavoprotein nature and enzymatic properties of the purified proteins. J. Biol. Chem. 256 (1981) 4109–4115. [PMID: 6163778]
5.  Porter, D.H., Cook, R.J. and Wagner, C. Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver. Arch. Biochem. Biophys. 243 (1985) 396–407. [PMID: 2417560]
6.  Brizio, C., Brandsch, R., Bufano, D., Pochini, L., Indiveri, C. and Barile, M. Over-expression in Escherichia coli, functional characterization and refolding of rat dimethylglycine dehydrogenase. Protein Expr. Purif. 37 (2004) 434–442. [PMID: 15358367]
7.  Brizio, C., Brandsch, R., Douka, M., Wait, R. and Barile, M. The purified recombinant precursor of rat mitochondrial dimethylglycine dehydrogenase binds FAD via an autocatalytic reaction. Int. J. Biol. Macromol. 42 (2008) 455–462. [PMID: 18423846]
8.  Luka, Z., Pakhomova, S., Loukachevitch, L.V., Newcomer, M.E. and Wagner, C. Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. Biochem. Biophys. Res. Commun. 449 (2014) 392–398. [PMID: 24858690]
9.  Augustin, P., Hromic, A., Pavkov-Keller, T., Gruber, K. and Macheroux, P. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant. FEBS J. 283 (2016) 3587–3603. [PMID: 27486859]
[EC 1.5.8.4 created 1972 as EC 1.5.99.2, transferred 2012 to EC 1.5.8.4, modified 2017]
 
 


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