Structural Consideration of the Working Mechanism of Fold Type I Transaminases From Eubacteria: Overt and Covert Movement

Abstract

Transaminases (TAs) reversibly catalyze the transfer reaction of an amino group between an amino group donor and an amino group acceptor, using pyridoxal 5′-phosphate (PLP) as a cofactor. TAs are categorized according to the amino group position of the donor substrate and respective TAs recognize their own specific substrates. Over the past decade, a number of TA structures have been determined by X-ray crystallography. On the basis of the structural information, the detailed mechanism of substrate recognition by TAs has also been elucidated. In this review, fold type I TAs are addressed intensively. Comparative studies on structural differences between the apo and holo forms of fold type I TAs have demonstrated that regions containing the active site exhibit structural plasticity in the apo form, facilitating PLP insertion into the active site. In addition, given that TAs recognize two different kinds of substrates, they possess dual substrate specificity. It is known that spatial rearrangements of active site residues occur upon binding of the substrates. Intriguingly, positively charged residues are predominantly distributed at the active site cavity. The electric field generated by such charge distributions may attract negatively charged molecules, such as PLP and amino group acceptors, into the active site. Indeed, TAs show remarkable dynamics in diverse aspects. In this review, we describe the comprehensive working mechanism of fold type I TAs, with a focus on conformational changes. Keywords: Transaminase, Pyridoxal 5′-phosphate, Dual substrate specificity, Conformational change, Transamination