Structural and biochemical analysis of Bacillus anthracis prephenate dehydrogenase reveals an unusual mode of inhibition by tyrosine via the ACT domain.

ABSTRACT: Tyrosine biosynthesis via the shikimate pathway is absent in humans and other animals, making it an attractive target for next-generation antibiotics, which is increasingly important due to the looming proliferation of multidrug-resistant pathogens. Tyrosine biosynthesis is also of commercial importance for the environmentally friendly production of numerous compounds, such as pharmaceuticals, opioids, aromatic polymers, and petrochemical aromatics. Prephenate dehydrogenase (PDH) catalyzes the penultimate step of tyrosine biosynthesis in bacteria: the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate. The majority of PDHs are competitively inhibited by tyrosine and consist of a nucleotide-binding domain and a dimerization domain. Certain PDHs, including several from pathog

SUBMITTER: Shabalin IG 

PROVIDER: S-EPMC7239764 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature