4GDN

Structure of FmtA-like protein

Summary for 4GDN

• Entry DOI: 10.2210/pdb4gdn/pdb
• Related: 3O3V
• Descriptor: Protein flp, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL (3 entities in total)
• Functional Keywords: peptidase, alpha/beta, hydrolase
• Biological source: Staphylococcus aureus
• Cellular location: Cell membrane; Multi-pass membrane protein (Potential): Q7A3Q5
• Total number of polymer chains: 4
• Total formula weight: 155164.02

Authors

Cougnoux, A.,Gibold, L.,Delmas, J.,Robin, F.,Dalmasso, G.,Bonnet, R. (deposition date: 2012-08-01, release date: 2012-10-03, Last modification date: 2023-09-13)

Primary citation

Cougnoux, A.,Gibold, L.,Robin, F.,Dubois, D.,Pradel, N.,Darfeuille-Michaud, A.,Dalmasso, G.,Delmas, J.,Bonnet, R.
Analysis of Structure-Function Relationships in the Colibactin-Maturating Enzyme ClbP.
J.Mol.Biol., 424:203-214, 2012

PubMed Abstract: pks genomic island of Escherichia coli is involved in the synthesis of the non-ribosomal peptide-type genotoxin colibactin, which has been suggesting as affecting the host immune response and having an impact on cancer development. The pks-encoded enzyme ClbP is an atypical peptidase that contributes to the synthesis of colibactin. In this work, we identified key features of ClbP. Bacterial fractionation and Western-blot analysis revealed the docking of ClbP to the bacterial inner membrane via a C-terminal domain harboring three predicted transmembrane helices. Whereas only one helix was necessary for the location in the inner membrane, the complete sequence of the C-terminal domain was necessary for ClbP bioactivity. In addition, the N-terminal sequence of ClbP allowed the SRP/Sec/YidC- and MreB-dependent translocation of the enzymatic domain in the periplasmic compartment, a feature also essential for ClbP bioactivity. Finally, the comparison of ClbP structure with that of the paralogs FmtA-like and AmpC revealed at an extremity of the catalytic groove a negative electrostatic potential surface characteristic of ClbP. Site-directed mutagenesis experiments identified in this zone two aspartic residues that were important for ClbP bioactivity. Overall, these results suggest a model for precolibactin activation by ClbP and pave a way for the design of inhibitors targeting colibactin production.

PubMed: 23041299
DOI: 10.1016/j.jmb.2012.09.017

Experimental method

X-RAY DIFFRACTION (3.2 Å)