Properties of bacterial and archaeal branched-chain amino acid aminotransferases

• Published in: Biochemistry (Moscow) Vol. 82; no. 13; pp. 1572 - 1591
• Main Authors: Bezsudnova, E. Yu, Boyko, K. M., Popov, V. O.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.12.2017; Springer
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Branched chain amino acids; Life Sciences; Microbiology; Review; Structure; Transaminases; dual substrate recognition; branched-chain amino acid aminotransferases (BCATs); bacterial and archaeal enzymes; substrate specificity; pyridoxal 5′-phosphate catalysis; 3D structure; characteristic sequence motifs
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297917130028

Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. BCATs are the key enzymes of BCAA metab- olism in all organisms. The catalysis proceeds through the ping-pong mechanism with the assistance of the cofactor pyri- doxal 5′-phosphate (PLP). BCATs differ from other ( S )-selective transaminases (TAs) in 3D-structure and organization of the PLP-binding domain. Unlike other ( S )-selective TAs, BCATs belong to the PLP fold type IV and are characterized by the proton transfer on the re-face of PLP, in contrast to the si -specificity of proton transfer in fold type I ( S )-selective TAs. Moreover, BCATs are the only ( S )-selective enzymes within fold type IV TAs. Dual substrate recognition in BCATs is imple- mented via the “lock and key” mechanism without side-chain rearrangements of the active site residues. Another feature of the active site organization in BCATs is the binding of the substrate α-COOH group on the P-side of the active site near the PLP phosphate group. Close localization of two charged groups seems to increase the effectiveness of external aldimine for- mation in BCAT catalysis. In this review, the structure-function features and the substrate specificity of bacterial and archaeal BCATs are analyzed. These BCATs differ from eukaryotic ones in the wide substrate specificity, optimal tempera- ture, and reactivity toward pyruvate as the second substrate. The prospects of biotechnological application of BCATs in stereoselective synthesis are discussed.