Fourteenth International Symposium on Recent Advances in Environmental Health Research POSTER SESSION B [FACULTY/SCIENTISTS]

9 | PB

THE STUDY OF PSEUDOMONAS RACEMASES FOR THE DRUG DESIGN AND BIOREMEDIATION PURPOSES

Hung-Chung Huang1,2, Ansley Scott2 and Paul B. Tchounwou1,2

1NIH/NIMHD RCMI Center for Environmental Heath, College of Science, Engineering, and Technology (CSET), Jackson State University, Jackson, MS 39217, USA 2Department of Biology, CSET, Jackson State University, Jackson, MS 39217, USA

Abstract: The Pseudomonas species have been the focus of research for decades. For example, Pseudomonas aeruginosa is an opportunistic pathogen and associated with serious cross-infections in the hospitals and clinics; and several Pseudomonas sp. (e.g., a safe species, P. putida) have the ability to be used in bioremediation to biodegrade oil. The D- produced by (AlaR) is used for peptidoglycan biosynthesis in bacteria, so AlaR is a good drug design target on P. aeruginosa. (MdlR) in P. putida is related to mandelate pathway that has something to do with the ability to degrade organic solvents such as toluene. In addition, both AlaR and MdlR utilize a similar catalytic mechanism. Therefore, the structural and comparative study of AlaR in P. aeruginosa and MdlR in P. putida would help us understand better the catalytic mechanism of both racemases which can contribute to the antibiotic drug design targeting P. aeruginosa and the application of bioremediation (via biodegradation) by Pseudomonas species like P. putida. Due to limited X-ray crystallography structure for the AlaR from P. aeruginosa (one available), ten AlaR high-resolution structures from Geobacillus stearothermophilus would be studied and compared to the one from P. aeruginosa for drug design purpose. Ten MdlR X-ray structures for P. putida were available from RCSB PDB databank and these ten structures would be studied and compared to those 11 AlaR structures mentioned above, in order to understand MdlR’s catalytic mechanism better for bioremediation purposes. We have used VMD program from UIUC to study the crystal water sites around the AlaR active sites via TCL scripting language, and used clustering program plus PERL & R to analyze and identify those conserved water sites important for enzymatic function. These conserved and stable water sites can be useful for drug design purposes targeting AlaR. The similar studies and analyses would be performed on those MdlR structures (to be compared to AlaR) to identify the conserved crystal water sites (around the ) which are related to and may play a big role in the ’s catalytic function. Due to the similarity of the catalytic mechanism in both AlaR and MdlR, the structural and comparative studies of these two racemases in bacteria can help us to be able to design a specific and potent drug targeting AlaR in P. aeruginosa and perform a capable bioremediation on spilled oil by bacteria like P. putida with a fine-tuned catalytic function of bioengineered and modified MdlR. Keywords: Pseudomonas aeruginosa, Alanine Racemase (AlaR), Pseudomonas putida, Mandelate Racemase (MdlR), cluster analysis, drug design, bioremediation. Acknowledgements: This research supported by the National Institutes of Health/National Institute on Minority Health and Health Disparities Grant #G12MD007581, through the RCMI Center for Environmental Health at Jackson State University.

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