The Gcn5-related N-acetyltransferase (GNAT) superfamily is composed of a vast number of species in all three kingdoms of life. They play essential roles in a wide variety of several metabolic and cellular processes such as: transcription, post-translational modifications, gene regulation, drug resistance, and detoxification. Although many GNAT enzymes have been studied, many remain to be structurally and functionally characterized. Since GNATs utilize diverse substrates, we are interested in learning more about how the acceptor site of these proteins has evolved to recognize these different substrates. We previously showed the PA2271 GNAT enzyme from Pseudomonas aeruginosa can acetylate spermine and spermidine in a broad-substrate screening assay, but it has not been further characterized and its native function is unknown. In this study, we designed spermine and spermidine substrate analogs to further probe PA2271 substrate specificity and enzymatic activity. These spermine and spermidine analogs were synthesized via a mono-protection of putrescine followed by nucleophilic substitution and deprotection. Ultimately, our goal is to co-crystallize PA2271 in complex with these substrate analogs to better delineate the acceptor substrate binding mechanism of PA2271 and aid in native function determination. Since polyamines are important for regulating growth within plants and bacteria and Pseudomonas aeruginosa resides in the rhizosphere of plants, we want to understand more about how this enzyme may participate in these processes.

Synthesis and characterization of potential substrates for PA2271 Gcn-5-related N-acetyltransferase

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