Researchers from the Seattle Structural Genomics Center for Infectious Disease (SSGCID) have determined the structure of the FabG protein from the Gram-negative bacterium Rickettsia prowazekii.
R. prowazekii causes epidemic typhus in humans, a disease that flourishes in areas suffering from overcrowding or poor hygiene, such as jails or refugee camps. This parasitic bacteria can only reproduce through host infection and is transmitted most commonly by contact with the saliva or feces of lice and fleas. Although louse control has succeeded in suppressing typhus in the modern era, recent outbreaks in the United States, Africa and Europe have established R. prowazekii as a re-emerging disease threat.
Owing to its small genome (about 800 protein-coding genes), R. prowazekii relies on the mammalian host for many basic biosynthetic processes, hindering the identification of potential anti-pathogenic drug targets. However, R. prowazekii metabolism depends upon the type II fatty-acid synthesis (FAS) pathway for lipogenesis (the conversion of acetyl-CoA to fats), as opposed to the type I FAS pathway utilized by humans.
FabG is the third enzyme in the FAS II pathway. The structure of FabG from Rickettsia is similar to structures from well-characterized pathogens such as Mycobacterium tuberculosis and Burkholderia pseudomallei. However, the structure of this protein differs significantly from the analogous mammalian structure, so drugs known to target the enzymes of pathogenic bacteria may serve as potential leads against Rickettsia. The SSGCID hopes that the l structural information provided for this Rickettsia FabG protein will aid scientists in identifying new strategies for the development of drugs and other therapeutics.
The structure was published in the journal Acta Cryst F, as one of 30 publications comprising one special edition focused solely on SSGCID work. Reference: Subramanian S, Abendroth J, Phan IQH, Olsen C, Staker BL, Napuli A et al. Crystal structure of 3-ketoacyl-(acyl-carrier-protein) reductase from Rickettsia prowazekii at 2.25 Ångström Resolution. Acta Cryst. 2011 Sep 1;67(Pt 9):1118-22. Epub 2011 Aug 16.
For more information, please see the Protein Data Bank entry 3F9I
Last Updated March 29, 2012
Last Reviewed March 29, 2012