3H93: Crystal Structure of Pseudomonas aeruginosa DsbA

Bacterial antibiotic resistance is an emerging global crisis, and treatment of multidrug-resistant gram-negative infections, particularly those caused by the opportunistic human pathogen Pseudomonas aeruginosa, remains a major challenge. This problem is compounded by a lack of new antibiotics in the development pipeline: only two new classes have been developed since the 1960s, and both are indicated for multidrug-resistant gram-positive infections. A promising new approach to combat antibiotic resistance is by targeting bacterial virulence, rather than bacterial viability. The bacterial periplasmic protein DsbA represents a central point for antivirulence intervention because its oxidoreductase activity is essential for the folding and function of almost all exported virulence factors. Here we describe the three-dimensional structure of this DsbA target from P. aeruginosa, and we establish for the first time that a member of this enzyme family is capable of binding small molecules. We also describe biochemical assays that validate the redox activity of PaDsbA. Together, the structural and functional characterization of PaDsbA provides the basis for future studies aimed at designing a new class of antivirulence compounds to combat antibiotic-resistant P. aeruginosa infection.
PDB ID: 3H93Download
MMDB ID: 78566
PDB Deposition Date: 2009/4/29
Updated in MMDB: 2009/12
Experimental Method:
x-ray diffraction
Resolution: 1.501  Å
Source Organism:
Similar Structures:
Biological Unit for 3H93: monomeric; determined by author and by software (PISA)
Molecular Components in 3H93
Label Count Molecule
Protein (1 molecule)
Thiol:disulfide Interchange Protein Dsba(Gene symbol: dsbA)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB