3h93 | pdb_00003h93
Crystal Structure of Pseudomonas aeruginosa DsbA
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacterial antibiotic resistance is an emerging global crisis and treatment of multi-drug 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 multi-drug 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 anti-virulence 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 anti-virulence compounds to combat antibiotic-resistant P. aeruginosa infection. Characterisation of the DsbA oxidative folding catalyst from Pseudomonas aerugionsa reveals a highly oxidizing protein that binds small molecules.,Shouldice SR, Heras B, Jarrott R, Sharma P, Scanlon MJ, Martin J Antioxid Redox Signal. 2009 Sep 29. PMID:19788398[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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