Diaminopimelate epimerase and

The amino acid sequences of known hydantoin racemases present two highly conserved cysteines around positions 75 and 180 (see the asterisks in Figure 12.4). The enzymes involved in the racemization/epimerization of different substrates such as glutamate racemase and diaminopimelate epimerase present two cyste-... 

In addition to n-alanine and n-glutamate, many bacterial cell walls also contain meso-diaminopimelate (DAP) [2]. DAP is produced by epimerization from l,l-DAP to d,l-DAP by the cofactor independent diaminopimelate epimerase [97, 98]. The structure of this enzyme has been solved and two cysteines in the active site were proposed to be the acid-base catalysts [99]. The pattern of label incorporation from tritiated water is consistent with a two-base mechanism [97]. The enzyme has been shown to be stoichiometrically inhibited by the thiol alkylating agent aziDAP [97]. Interestingly, DAP epimerase has an equilibrium constant of 2 (Keq = [d,l]/[l,l]) duc to the statistically expected higher concentration of the [d,l] form at equilibrium between these species [100]. 

Cirilli et al.11171 cloned the gene of diaminopimelate epimerase from Haemophilus influenzae, and purified and crystallized the enzyme. The enzyme is monomeric and has a unique protein fold, in which the amino terminal and carboxyl terminal halves of the molecule fold into structurally homologous and superimposable domains (Fig. 17-13). Cys 73 of the amino terminal domain is found in the disulfide linkage, at the domain interface, with Cys 217 of the carboxy terminal domain 117. Thus, it is most conceivable that these two cysteine residues stay in reduced form in the active enzyme and function as the acid and base in the mechanism. Koo and Blanchard 118 explored a number of kinetic and isotope approaches to clarify the mechanism of the enzyme. However, which of the two cysteine residues is responsible for proton abstraction from the two enantiomeric Ca-H bonds is not yet known. 

Bartlett, A.T.M. and White, P.J. (1985) Species of Bacillus that make a vegetative peptidoglycan containing lysine lack diaminopimelate epimerase but have diaminopimelate dehydrogenase. 

This approach was utilized by Gelb and Vederas in a synthesis of the fluorinated amino acid 53, an inhibitor of diaminopimelate epimerase (Scheme 10.6) [56],... 

Diaminopimelate decarboxylase catalyzes the final step in lysine biosynthesis in bacteria. The epimerase catalyzes the interconversion of the ll- and meso isomers of diaminopimelate. Because these enzymes are absent in mammals, they are considered to be potential targets for antimicrobial agents. 

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