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Literature summary for 1.4.9.1 extracted from

  • Wilmot, C.; Yukl, E.
    MauG A di-heme enzyme required for methylamine dehydrogenase maturation (2013), Dalton Trans., 42, 3127-3135 .
No PubMed abstract available

Activating Compound

Activating Compound Comment Organism Structure
MauG the di-heme enzyme is required for methylamine dehydrogenase maturation. MauG is highly unusual in that the di-ferrous c-type heme redox state can also bind and activate O2. Mixing preMADH with either di-ferric MauG and H2O2 or di-ferrous MauG and O2, leads to fully active MADH. Thus, MauG represents the final enzyme in MADH maturation, catalyzing a 6-electron oxidation to complete tryptophan tryptophyquinone, TTQ, biosynthesis. Upon reaction of di-ferric MauG with H2O2, an unprecedented high-valent species is formed, which Mossbauer spectroscopy showed contains both MauG hemes in the Fe(IV) oxidation state. Analysis of the crystal structure of MauG in complex with preMADH at 2.1 resolution, overview. MauG reaction mechanism and kinetics with preMADH and H2O2. MauG-dependent completion of TTQ biosynthesis requires a hole hopping electron transfer mechanism. Structure-function analysis. The MauG Y294H variant is unable to catalyze TTQ biosynthesis Paracoccus denitrificans

Cloned(Commentary)

Cloned (Comment) Organism
the methylamine utilization (mau) gene cluster contains 11genes, two of which encode the 42.5 kDa alpha-(mauB) and the 14.2 kDa beta-subunits (mauA) of MADH, recombinant co-overexpression of genes mauAB in Rhodobacter sphaeroides in the presence of mauDEFG, the four genes required for MADH maturation results in an alpha2beta2 MADH protein that has no catalytic activity, because the protein contains all six beta-subunit disulfides, but has a partially synthesized TTQ cofactor with only a single -OH group added to the indole of betaTrp57 (betaTrp57-OH) Paracoccus denitrificans

Crystallization (Commentary)

Crystallization (Comment) Organism
MauG in complex with preMADH, X-ray diffraction structure determination and analysis at 2.1 resolution Paracoccus denitrificans

Localization

Localization Comment Organism GeneOntology No. Textmining
periplasm
-
Paracoccus denitrificans
-
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
114000
-
-
Paracoccus denitrificans

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
methylamine + H2O + 2 amicyanin Paracoccus denitrificans
-
formaldehyde + NH3 + 2 reduced amicyanin
-
?

Organism

Organism UniProt Comment Textmining
Paracoccus denitrificans P22619 AND P29894 alpha and beta subunits encoded by genes mauA and mauB
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Posttranslational Modification

Posttranslational Modification Comment Organism
additional information tryptophan tryptophyquinone, TTQ, the catalytic cofactor of enzyme MADH is not an exogenous cofactor but is instead derived from posttranslational modifications of the beta subunits of MADH via 8-electron oxidation of two specific tryptophans in the MADH beta-subunit, betaTrp57 and betaTrp108. The final 6-electron oxidation is catalyzed by the unusual c-type di-heme enzyme, MauG. reMADH has essentially the same structure as mature MADH, with preTTQ betaTrp108 coincident with its position in TTQ, and the plane of the betaTrp57-OH indole rotated about 20° from its position in TTQ Paracoccus denitrificans

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
methylamine + H2O + 2 amicyanin
-
Paracoccus denitrificans formaldehyde + NH3 + 2 reduced amicyanin
-
?
additional information methylamine dehydrogenase (MADH) requires the cofactor tryptophan tryptophylquinone (TTQ) for activity Paracoccus denitrificans ?
-
?

Subunits

Subunits Comment Organism
heterotetramer alpha2beta2, 2 * 42500, alpha-subunit, + 2 * 14200, beta-subunit, SDS-PAGE Paracoccus denitrificans
More MADH is a 114 kDa alpha2beta2 heterotetramer with two independent active sites, each containing a TTQ cofactor biosynthesized from betaTrp57 and betaTrp108 of the beta-subunit Paracoccus denitrificans

Synonyms

Synonyms Comment Organism
MADH
-
Paracoccus denitrificans
methylamine dehydrogenase
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Paracoccus denitrificans

Cofactor

Cofactor Comment Organism Structure
tryptophan tryptophylquinone TTQ, methylamine dehydrogenase requires the cofactor tryptophan tryptophylquinone for activity. TTQ is a posttranslational modification that results from an 8-electron oxidation of two specific tryptophans in the MADH beta-subunit, betaTrp57 and betaTrp108. The final 6-electron oxidation is catalyzed by the unusual c-type di-heme enzyme, MauG. The di-ferric enzyme can react with H2O2, but atypically for c-type hemes the di-ferrous enzyme can react with O2 as well. In both cases, an unprecedented bis-Fe(IV) redox state is formed, composed of a ferryl heme (Fe(IV)=O) and the second heme as Fe(IV) stabilized by His-Tyr axial ligation. Bis-Fe(IV) MauG acts as a potent 2-electron oxidant. Catalysis is long-range and requires a hole hopping electron transfer mechanism. TTQ structure analysis, overview Paracoccus denitrificans

General Information

General Information Comment Organism
malfunction the genes mauF and mauE are membrane proteins with no homology to characterized proteins, and are thought to be involved in transport of MADH subunits into the periplasm. Knocking out either gene leads to no detectable beta-subunit in the periplasm, and an unusual beta-subunit leader sequence is consistent with it being trafficked by a specific transporter. The loss of mauF and mauE additionally leads to a drastic reduction in alpha-subunit. The third gene, mauD, is homologous to disulfide isomerases, and is likely specific to the MADH beta-subunit, which has six disulfides. In the absence of mauD, periplasmic alpha-subunit levels are close to normal, but again there is no detectable beta-subunit implying that the disulfides are key to beta-subunit stability. When the final required gene, mauG, is knocked out, there are normal levels of MADH alpha- and beta-subunit in the periplasm, but no methylamine dehydrogenase activity is present. This has focused attention on the mauG gene product as a likely participant in TTQ biosynthesis Paracoccus denitrificans