Document Type
Article
Publication Date
5-2014
Publication Title
PLOS One
Volume
9
Issue
5
Pages
1-11
Publisher Name
PLOS
Abstract
The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Thereforedap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) convertsN-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate.
Recommended Citation
Nocek B, Starus A, Makowska-Grzyska M, Gutierrez B, Sanchez S, et al. (2014) The Dimerization Domain in DapE Enzymes Is required for Catalysis. PLoS ONE 9(5): e93593. doi:10.1371/journal.pone.0093593
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Statement
© 2014 Nocek et al.
Comments
Author Posting. © 2014 Nocek et al. This article is posted here by permission of the authors for personal use, not for redistribution. The article was published in PLOS One, May 2014, http://dx.doi.org/10.1371/journal.pone.0093593