Kinetic, spectral, and structural studies of the slow-binding inhibition of the Escherichia coli dihydrodipicolinate synthase by 2, 4-oxo-pentanoic acid.

ABSTRACT: Dihydrodipicolinate synthase (DHDPS) catalyzes the first step in the biosynthetic pathway for production of l-lysine in bacteria and plants. The enzyme has received interest as a potential drug target owing to the absence of the enzyme in mammals. The DHDPS reaction is the rate limiting step in lysine biosynthesis and involves the condensation of l-aspartate-β-semialdehyde and pyruvate to form 2, 3-dihydrodipicolinate. 2, 4-oxo-pentanoic acid (acetopyruvate) is a slow-binding inhibitor of DHDPS that is competitive versus pyruvate with an initial K_i of about 20 μM and a final inhibition constant of about 1.4 μM. The enzyme:acetopyruvate complex displays an absorbance spectrum with a λ_max at 304 nm and a longer wavelength shoulder. The rate constant for formation of the

SUBMITTER: Karsten W 

PROVIDER: S-EPMC8592399 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature