Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes

Abstract

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are ubiquitous, catalyzing various biochemical reactions of approximately 4% of all classified enzymatic activities. They transform amines and amino acids into important metabolites or signaling molecules and are important drug targets in many diseases. In the crystal structures of PLP-dependent enzymes, organic cofactor PLP showed diverse conformations depending on the catalytic step. The conformational change of PLP is essential in the catalytic mechanism. In the study, we review the sophisticated catalytic mechanism of PLP, especially in transaldimination reactions. Most drugs targeting PLP-dependent enzymes make a covalent bond to PLP with the transaldimination reaction. A detailed understanding of organic cofactor PLP will help develop a new drug against PLP-dependent enzymes. [BMB Reports 2022; 55(9): 439-446]

Reductive amination cascades in cell-free and resting whole cell formats for valorization of lignin deconstruction products

“…These multidomain enzymes first catalyze the adenylation of carboxylic acids using ATP in the N-terminal adenylation domain, next form a thioester on a phosphopantheinyl swinging arm in the thiolation domain, and finally catalyze the formation of an aldehyde at the expense of NADPH in the C-terminal reduction domain. The ωTAs are pyridoxal 5’-phosphate (PLP)-dependent enzymes that have previously been applied to reversibly catalyze amination by transferring an amine group from an amine donor to the substrate aldehyde or ketone through a pyridoxamine 5’-phosphate (PMP) intermediate (Höhne and Bornscheuer, 2009; Ngo et al, 2022; Rocha et al, 2019). Recently, we reported bioprospecting of diverse CAR enzymes and their coupling to the well-known ω-TA from Chromobacter violaceum (cvTA) to build a one-pot cascade for highly selective and efficient conversion of deconstruction product from polyethylene terephthalate (PET) to mono-and diamines (Gopal et al, 2023).…”

Reductive amination cascades in cell‐free and resting whole cell formats for valorization of lignin deconstruction products

“…The TAs are pyridoxal 5'-phosphate (PLP)-dependent enzymes that have previously been applied to reversibly catalyze amination by transferring an amine group from an amine donor to the substrate aldehyde or ketone through a pyridoxamine 5'-phosphate intermediate (Höhne & Bornscheuer, 2009;Ngo et al, 2022;Rocha et al, 2019).…”

“…These multidomain enzymes first catalyze the adenylation of carboxylic acids using ATP in the N‐terminal adenylation domain, next form a thioester on a phosphopantheinyl swinging arm in the thiolation domain, and finally catalyze the formation of an aldehyde at the expense of NADPH in the C‐terminal reduction domain. The TAs are pyridoxal 5'‐phosphate (PLP)‐dependent enzymes that have previously been applied to reversibly catalyze amination by transferring an amine group from an amine donor to the substrate aldehyde or ketone through a pyridoxamine 5'‐phosphate intermediate (Höhne & Bornscheuer, 2009; Ngo et al, 2022; Rocha et al, 2019). Recently, we reported bioprospecting of diverse CAR enzymes and their coupling to the well‐known ω‐TA from Chromobacter violaceum (cvTA) to build a one‐pot cascade for highly selective and efficient conversion of deconstruction product from polyethylene terephthalate (PET) to mono‐and diamines (Gopal et al, 2023).…”