Decarboxylase dialkylglycine

Chruma JJ, Liu L, Zhou W, Breslow R. Hydrophobic and electronic factors in the design of dialkylglycine decarboxylase mimics. Bioorg. Med. Chem. 2005 13 5873-5883. 

Lysine is formed in bacteria by decarboxylation of meso-diamino-pimelic acid (Fig. 24-14). Glycine is decarboxylated oxidatively in mitochondria in a sequence requiring lipoic acid and tetrahydrofolate as well as PLP (Fig. 15-20). A methionine decarboxylase has been isolated in pure form from a fem. ° The bacterial dialkylglycine decarboxylase is both a decarboxylase and an aminotransferase which uses pyruvate as its second substrate forming a ketone and L-alanine as products (See Eq. 

Dialkylglycine decarboxylase (DGD) is unusual as it catalyzes both a decarboxylation and a transamination during its normal catalytic cycle. DGD uses stereoelectronic effects to control its unusual reaction specificity. The three-dimensional structure of DGD showed that the enzyme possesses two binding sites for monovalent cations (MVCs). In particular, one site, located near the active site, hinds potassium ions and controls the catalytic activity. The other is located at the carboxyl terminus of an alpha helix and prohahly has a structural role. 

Within each of these sublineages, the type of catalyzed reaction was mostly conserved, whereas the substrates varied. For example, all the enzymes in the ATII subfamily are aminotransferases, with the only apparent exception of dialkylglycine decarboxylase, which, however, catalyzes a decarboxylation-dependent transamination (the enzyme cannot directly transaminate its substrate, which lacks an ct-proton, but proceeds to decarboxylate it and then catalyzes a transamination with the decarboxylation product)." Hence, the evolutionary tree shows that, in general, specialization for reaction type came first, whereas the last and shortest phase of the evolutionary history involved specialization for substrate specificity. 

W. Liu, C. J. Rogers, A. J. Fisher, M. D. Toney, Biochemistry 2002, 41, 12320-12328. Aminophosphonate inhibitors of dialkylglycine decarboxylase structural basis for slow binding inhibition. 

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