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Structure of the Month: Francisella tularensis serine hydrolase

Francisella tularensis is a bacterium that causes tularemia, a naturally occurring disease in the United States and parts of Europe and Asia. Tularemia is also known as rabbit fever or deerfly fever. Humans are susceptible to infection typically via insect bites, inhalation of bacteria, and exposure to infected animals. Because of the low number of bacteria required for infection and potential use as a biowarfare agent, Francisella tularensis has received renewed scientific interest in recent years. Current treatment options utilize the broad-spectrum antibiotics tetracycline and streptomycin. A new therapeutic approach could involve an emerging class of novel antibacterial targets: enzymes known as serine hydrolases. This large class of highly conserved enzymes is essential to the virulence of the bacterium.

The Center for Structural Genomics of Infectious Diseases has determined the three-dimensional structure of one of these serine hydrolases, the FTT258 carboxylesterase protein from a highly virulent human strain: Francisella tularensis SCHU S4. The protein has been captured in both an open and a closed conformation. In one of the molecules shown, a novel cyclobutanone inhibitor is bound to a serine, confirming the proposed active site. The open and closed conformations of FTT258 give insight as to how the protein interacts with its substrates and how it may localize within the cell.

More information can be found using the Protein Data Bank code 4F21.

F. tularemia serine hydrolase structure

Figure legend: Superposition of two FTT258 protein molecules in a closed (violet) and open (green) form. Tryptophan and tyrosine residues on the mobile loop are shown. The inhibitor is bound to the open form and it is shown as a ball and stick model (magenta).

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Last Updated September 13, 2012

Last Reviewed September 13, 2012