Structure, Dynamics and Function of AlgH

University Of Georgia, Athens GA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The goal of the research is to delineate the structure, stability, dynamics and method of function of the novel transcriptional regulator AlgH from Pseudomonas aeruginosa. Pseudomonas aeruginosa is the quintessential opportunistic pathogen, responsible for many devastating infections, including those most often linked to cystic fibrosis, and is renowned for its antibiotic resistance. This resistance is conferred in part by biosynthesis of alginate, an exomucopolysaccharide protectant and virulence factor. AlgH is a unique regulator of many functions in Pseudomonas aeruginosa, including alginate biosynthesis, and is the namesake of an uncharacterized family of bacterial proteins with no sequence homologues outside of the family. Recent unpublished results also suggest a critical link between AlgH and biofilm development. The proposed studies are essential to define the method of AlgH function and the physical underpinnings in order to effect pharmaceutical development and comparative studies of other AlgH family members. The aims are to determine the structure of AlgH at high resolution in solution using progressive NMR methods including leading-edge dipolar coupling techniques, to characterize the stability and dynamics of AlgH using hydrogen exchange and nuclear spin-relaxation techniques, and to unambiguously identify AlgH binding partners using mass spectrometry based identification. The results will be of general importance for prokaryotic genomics and bacteriology, and are likely to be of substantial general importance for our understanding of protein structure and function. [unreadable] [unreadable]