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B6db references: 26921318

type Journal Article
authors Peverelli MG, Soares da Costa TP, Kirby N, Perugini MA
title Dimerization of bacterial diaminopimelate decarboxylase is essential for catalysis
journal J Biol Chem
sel selected
ui 26921318
year (2016)
volume 291
number 18
pages 9785-95
keywords analytical ultracentrifugation; diaminopimelate decarboxylase; dimerization; enzyme; enzyme kinetics; lysine biosynthesis; small-angle X-ray scattering (SAXS)
abstract Diaminopimelate decarboxylase (DAPDC) catalyzes the final step in the diaminopimelate biosynthesis pathway of bacteria. The product of the reaction is the essential amino acid l-lysine, which is an important precursor for the synthesis of the peptidoglycan cell wall, housekeeping proteins, and virulence factors of bacteria. Accordingly, the enzyme is a promising antibacterial target. Previous structural studies demonstrate that DAPDC exists as monomers, dimers, and tetramers in the crystal state. However, the active oligomeric form has not yet been determined. We show using analytical ultracentrifugation, small angle x-ray scattering, and enzyme kinetic analyses in solution that the active form of DAPDC from Bacillus anthracis, Escherichia coli, Mycobacterium tuberculosis, and Vibrio cholerae is a dimer. The importance of dimerization was probed further by generating dimerization interface mutants (N381A and R385A) of V. cholerae DAPDC. Our studies indicate that N381A and R385A are significantly attenuated in catalytic activity, thus confirming that dimerization of DAPDC is essential for function. These findings provide scope for the development of new antibacterial agents that prevent DAPDC dimerization.
last changed 2017/12/19 10:11

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