Aminotransferases Aspartate aminotransferase family

The (I( )-l-amino-2-propanol linker is known to be derived from threonine. In S. enterica, CobD was found to be an enzyme with L-threonine 0-3-phosphate decarboxylase activity, which generates (/f)-l-amino-2-propa-nol phosphate. The enzyme is a pyridoxal phosphate requiring enzyme and the structure of the protein has been determined by X-ray crystallography (Figure 28). The structure of CobD was found to be highly similar to the aspartate aminotransferase family of enzymes. Structures of CobD with substrate and product bound have allowed a detailed mechanism for the enzyme to be proposed, whereby the external aldimine is directed toward decarboxylation rather than aminotransfer. Threonine phosphate, itself, is synthesized from L-threonine by the action of a kinase, which is encoded by pduX The pduX is housed within the propanediol utilization operon rather than the cobalamin biosynthetic operon for reasons that are not clear. 

Aspartate Aminotransferase Is a Member of a Large and Versatile Family of Pyridoxal-Dependent Enzymes... 

Aspartate aminotransferase is the prototype of a large family of PLP-dependent enzymes. Comparisons of amino acid sequences as well as several three-dimensional structures reveal that almost all transaminases having roles in amino acid biosynthesis are related to aspartate aminotransferase by divergent evolution. An examination of the aligned amino acid sequences reveals that two residues are completely conserved. These residues are the lysine residue that forms the Schiff base with the pyridoxal phosphate cofactor (lysine 258 in aspartate aminotransferase) and an arginine residue that interacts with the a-carboxylate group of the ketoacid (see Figure 23.11). 

Fig. 86. Coupling of enzyme reactions for the design of a sensor family based on LMO. CK = creatine kinase, PK = pyruvate kinase, MDH = malate dehydrogenase, PEP = phosphoenolpyruvate, ALAT = alanine aminotransferase, ASAT = aspartate aminotransferase.

Homology sequence modeling between ALAS and enzymes of the a-family of PLP-dependent enzymes indicated that arginine-439 (R439) of murine ALAS2 is a conserved residue in this family of PLP-dependent enzymes (Figure 2-5). Moreover, this conserved arginine in several enzymes, e.g. aspartate aminotransferase, for... 

Since the substrate specificity of individual aminotransferases may vary widely, it is not known whether the nitrogen atoms of the aspartate family and branched-chain amino acids are derived from a single, or from multiple precursors (Table I). Utilization of a common amino donor in aminotransferase catalyzed reactions would strengthen the biosynthetic relationship among the pathway products, whereas multiple precursors could tend to balance the synthesis of these amino acids with that of other protein precursors in a type of crosspathway or interfamily regulation. 

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