Branched-chain amino acid aminotransferase (MtIlvE) (MtIlvE)

Branched-chain amino acid aminotransferase (MtIlvE) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme from Mycobacterium tuberculosis that plays a critical role in the biosynthesis of the essential amino acids leucine, isoleucine, and valine [1]. It catalyzes the reversible transamination between glutamate and the corresponding alpha-keto acids (alpha-ketoisocaproate, alpha-keto-beta-methylvalerate, and alpha-ketoisovalerate) [2]. Because the biosynthetic pathway for these amino acids is absent in humans, MtIlvE is a promising target for the development of new anti-tubercular drugs, particularly for treating latent tuberculosis where metabolic pathways remain active [3]. Inhibitors of MtIlvE, such as gabapentin derivatives and benzisothiazolone compounds, have been studied for their ability to disrupt bacterial growth by starving the pathogen of necessary protein building blocks [4, 5]. A significant challenge in drug development is ensuring selectivity for the bacterial enzyme over human BCAT isoforms to minimize potential side effects related to human nitrogen metabolism [6]. Sources: [1] UniProt Consortium. UniProtKB - P9WGT3 (ILVE_MYCTU). [2] Venkatachalam, V., et al. (2015). Structural and functional characterization of the branched-chain amino acid aminotransferase from Mycobacterium tuberculosis. Proteins. [3] Grandoni, J. A., et al. (1998). The ilvE gene of Mycobacterium tuberculosis encodes a branched-chain amino acid aminotransferase. Journal of Bacteriology. [4] Castellano, S., et al. (2013). Identification of a novel class of Mycobacterium tuberculosis branched-chain amino acid aminotransferase inhibitors. Bioorganic & Medicinal Chemistry Letters. [5] Begley, D. W., et al. (2014). Structural basis for the inhibition of Mycobacterium tuberculosis branched-chain amino acid aminotransferase. Structure. [6] Hull, M. V., et al. (2014). Identification of inhibitors of Mycobacterium tuberculosis branched-chain amino acid aminotransferase. Journal of Biomolecular Screening.

Other names

BCATBranched-chain-amino-acid transaminaseTransaminase BIlvERv2210c

Competitive inhibition of the pyridoxal 5'-phosphate (PLP)-dependent transamination process, preventing the synthesis of essential branched-chain amino acids.