Valentina Di Francescovdifrancesco@niaid.nih.gov
Aldose reductase (AR) enzymes play a role in the conversion of glucose and are found across all families of life. In humans, ARs have been studied as targets for drugs to treat diseases such as diabetes. Now, scientists from the Seattle Structural Genomics Center for Infectious Diseases (SSGCID) have determined the structure of AR in Giardia lamblia in the hopes that the enzyme could be a possible target for the treatment of infectious diseases too.
Giardia is a protozoan parasite which causes the disease giardiasis and lives inside the small intestines of infected humans or other vertebrates. Individuals become infected through ingesting food, soil, or water contaminated by Giardia-infected feces. SSGCID researchers found that like other aldose reductases, the Giardia protein adopts an 8-stranded barrel structure. When compared to the human version of this enzyme, subtle variations can be observed in the substrate binding pocket, while the amino acids responsible for catalysis are highly conserved.
In humans, aldose reductase primarily functions in the conversion of glucose to fructose. In diabetics, aldose reductase is responsible for causing complications by converting excess glucose to sorbitol leading to osmotic swelling. Because of this role in disease, human aldose reductase has been the subject of intense study and numerous pharmaceuticals have been developed to inhibit its function. By studying the AR structure from a pathogen like Giardia, it is hoped that existing pharmaceutical research can be leveraged to finding new treatments of infectious diseases.
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: "Structure of aldose reductase from Giardia lamblia.." Ferrell, M., Abendroth, J., Zhang, S., Sankaran, B., Edwards, T.E., Staker, B.L, Van Voorhis, W.C., Stewart, L.J., and Myler, P.J. Acta Cryst. (2011) F67, 9:1113-1117 (PDF). PMID: 21904059.
For more information, please see the Protein Data Bank entry ID 3KRB.
Last Updated February 02, 2012
Last Reviewed February 02, 2012