TY - JOUR
T1 - Bacterial Branched-Chain Amino Acid Biosynthesis
T2 - Structures, Mechanisms, and Drugability
AU - Amorim Franco, Tathyana M.
AU - Blanchard, John S.
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/11/7
Y1 - 2017/11/7
N2 - The eight enzymes responsible for the biosynthesis of the three branched-chain amino acids (l-isoleucine, l-leucine, and l-valine) were identified decades ago using classical genetic approaches based on amino acid auxotrophy. This review will highlight the recent progress in the determination of the three-dimensional structures of these enzymes, their chemical mechanisms, and insights into their suitability as targets for the development of antibacterial agents. Given the enormous rise in bacterial drug resistance to every major class of antibacterial compound, there is a clear and present need for the identification of new antibacterial compounds with nonoverlapping targets to currently used antibacterials that target cell wall, protein, mRNA, and DNA synthesis.
AB - The eight enzymes responsible for the biosynthesis of the three branched-chain amino acids (l-isoleucine, l-leucine, and l-valine) were identified decades ago using classical genetic approaches based on amino acid auxotrophy. This review will highlight the recent progress in the determination of the three-dimensional structures of these enzymes, their chemical mechanisms, and insights into their suitability as targets for the development of antibacterial agents. Given the enormous rise in bacterial drug resistance to every major class of antibacterial compound, there is a clear and present need for the identification of new antibacterial compounds with nonoverlapping targets to currently used antibacterials that target cell wall, protein, mRNA, and DNA synthesis.
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U2 - 10.1021/acs.biochem.7b00849
DO - 10.1021/acs.biochem.7b00849
M3 - Review article
C2 - 28977745
AN - SCOPUS:85033386915
SN - 0006-2960
VL - 56
SP - 5849
EP - 5865
JO - Biochemistry
JF - Biochemistry
IS - 44
ER -