3H93

Crystal Structure of Pseudomonas aeruginosa DsbA

Summary for 3H93

• Entry DOI: 10.2210/pdb3h93/pdb
• Descriptor: Thiol:disulfide interchange protein dsbA, GLYCEROL (3 entities in total)
• Functional Keywords: disulfide bond, redox-active center, transcription regulator
• Biological source: Pseudomonas aeruginosa PAO1
• Cellular location: Periplasm : P0C2B2
• Total number of polymer chains: 1
• Total formula weight: 22017.22

Authors

Shouldice, S.R. (deposition date: 2009-04-29, release date: 2009-12-08, Last modification date: 2024-11-20)

Primary citation

Shouldice, S.R.,Heras, B.,Jarrott, R.,Sharma, P.,Scanlon, M.J.,Martin, J.L.
Characterization of the DsbA Oxidative Folding Catalyst from Pseudomonas aeruginosa Reveals a Highly Oxidizing Protein that Binds Small Molecules.
Antioxid Redox Signal, 12:921-931, 2010

PubMed Abstract: 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.

PubMed: 19788398
DOI: 10.1089/ars.2009.2736

Experimental method

X-RAY DIFFRACTION (1.501 Å)