Chemistry

An Investigation of the Unique Structural Forms of a Bacterial Enzyme

Presenter Information

Perry Rabin, Butler University

Document Type

Poster Presentation

Location

Indianapolis, IN

Subject Area

Chemistry

Start Date

11-4-2014 8:30 AM

End Date

11-4-2014 9:30 AM

Description

Francisella tularensis is a highly infectious bacterium and the causative agent of tularemia. In this project, two different structural forms of FTT258, a serine hydrolase from F. tularensis, were investigated as potential novel drug targets. Specifically, the two distinct structural forms (closed and open) were studied to determine their role in controlling the biological function of FTT258. For these studies, wild type FTT258 was isolated by heterologous expression in Escherichia coli and purification by Ni-metal affinity chromatography. The various protein conformations of FTT258 were then separated by size exclusion chromatography and the relative ratio of the open versus closed forms of FTT258 compared across various conditions. The closed to open form transition was found to be sensitive to time, temperature, and amino acid sequence, suggesting tight cellular control over this transition. The results of these experiments will have direct applications in understanding the regulation of FTT258.

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Apr 11th, 8:30 AM Apr 11th, 9:30 AM

An Investigation of the Unique Structural Forms of a Bacterial Enzyme

Indianapolis, IN

Francisella tularensis is a highly infectious bacterium and the causative agent of tularemia. In this project, two different structural forms of FTT258, a serine hydrolase from F. tularensis, were investigated as potential novel drug targets. Specifically, the two distinct structural forms (closed and open) were studied to determine their role in controlling the biological function of FTT258. For these studies, wild type FTT258 was isolated by heterologous expression in Escherichia coli and purification by Ni-metal affinity chromatography. The various protein conformations of FTT258 were then separated by size exclusion chromatography and the relative ratio of the open versus closed forms of FTT258 compared across various conditions. The closed to open form transition was found to be sensitive to time, temperature, and amino acid sequence, suggesting tight cellular control over this transition. The results of these experiments will have direct applications in understanding the regulation of FTT258.