Enzyme methylamine dehydrogenase

The enzyme methylamine dehydrogenase catalyzes the oxidation of amino-methane to formaldehyde according to the following equation ... 

This quantum analysis was systematized within the vibrationally enhanced ground-state tunneling theory (VEGST) (Bruno Bialek, 1992), experimentally verified on reactions catalyzed by the bacterial enzyme methylamine dehydrogenase (Basran et al., 1999), despite some limitations for those enzyme in which the tunneling process acts so close... 

Methylamine dehydrogenase [MADH] is a periplasmic enzyme which has been purified from several gram negative methylotrophic and autotrophie bacteria (reviewed in Davidson, 1993 Davidson et al, 1995a). It catalyzes the oxidation of methylamine to formaldehyde and ammonia, and in the proeess transfers two electrons from the substrate to some electron acceptor (Eq. 1). This reaetion is the first step in the metabolism of methylamine, whieh ean... 

McIntire,W. S., Wemmer, D. E., Christoserdov, A. Y., and Lindstrom, M. E., 1991, A new cofactor in a prokaryotic enzyme Tryptophan tryptophylquinone as the redox prosthetic group in methylamine dehydrogenase, Science 252 817n824. 

The direct electronic communication of this series of redox enzymes allows their application as bioactive sensing interfaces p-cresol [12], methylamine [14] and fructose [ 15] detection have been reported in the presence ofp-cresol methyl hydroxylase, methylamine dehydrogenase and fructose dehydrogenase, respectively. 

Methylamine dehydrogenase (MADH) catalyses the oxidative conversion of primary amines to aldehyde and ammonia. This enzyme is found in several methylotrophic bacteria that use amines as their principal source of carbon and energy. Experiments show unusually large primary kinetic isotope effects for the rate-limiting proton transfer step in the MADH reaction. These results imply that there is a large contribution to the proton transfer reaction from quantum tunnelling. Experiments also show that there is almost no dependence of the primary kinetic isotope effect on temperature for the methylamine substrate.151... 

Galactose oxidase has a unique tertiary structure for a copper protein, comparable with that of the non-copper protein methylamine dehydrogenase. Comparisons of the amino acid sequences [157] show, however, that the enzymes are not phylogenetically related. The tertiary structures developed separately [30]. 

Figure 5 Structure of the TTQ cofactor in methylamine dehydrogenase from P. denitrificans. In this enzyme oxygenation of /3Trp57 and cross-linking with /3Trp108 yields the TTQ cofactor, which is displayed as sticks colored gray for carbon, red for oxygen, and blue for nitrogen. The coordinates from PDB entry 2bbk were used to display this structure.

These cross-linked amino acid residues appear to have no direct participation in the catalytic mechanism. They do play a structural role in determining the tertiary structure of the 7 suhunit. It is interesting to note that the TTQ dependent methylamine dehydrogenase does not have these thioether cross-linked residues, but does have six intra-subunit disulfide bonds between cysteine residues, which play a structural role in determining the tertiary structure of the TTQ bearing (3 subunit of that enzyme. The a subunit of QHNDH contains two r-type hemes. One heme c is solvent-accessible and the other is fully buried within the a subunit and located approximately 9 A from the tryptophylquinone moiety of CTQ on the 7 subunit. The a and 7 subunits sit on the surface of the / subunit that with the 7 subunit forms the enzyme active site. 

The vast majority of amino acid dehydrogenases use ammonium ions as the amine donor. However, recently a novel N-methyl-L-amino acid dehydrogenase (NMAADH), from Pseudomonas putida, was isolated and used to synthesize N-methyl-L-phenylalanine 36 from phenylpyruvic acid 31 and methylamine 35 in 98% yield and greater than 99%e.e. (Scheme 2.15). The enzyme was shown to accept a number of different ketoacids and also use various amine donors. Glucose dehydrogenase from Bacillus suhtilis was used to recycle the NADPH cofactor [17]. 

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