Scientists from the Seattle Structural Genomics Center for Infectious Disease (SSCGID), in collaboration with researchers from Queen’s University, have determined the crystal structure of a key protein from the citric acid cycle, or Kreb’s cycle. This cycle enables cells to generate energy. Researchers studied the enzyme, isocitrate dehydrogenase (ICDH) which converts isocitrate to a-ketoglutarate and carbon dioxide in the third step of the cycle. They determined the structure of ICDH from Burkholderia pseudomallei (Bp) (BupsA.00092.a, PDB entry 3DMS), a naturally occurring soil-dwelling Gram-negative bacterium and potential bioterror agent. Bp causes acute and chronic melioidosis, which results in skin infections, chest, bone and joint pain, cough, lung nodules and enables contraction of pneumonia. The scientists found that Bp ICDH exhibits structural elements different from human ICDH. These differences allow Bp ICDH to be regulated by the enzyme AceK. Increased understanding of the pathogenic enzyme could help researchers identify future targets for the development of therapeutics against meliodosis.
For more information, please see Protein Data Bank entry 3DMS.
“Structural basis of substrate specificity of bifunctional isocitrate dehydrogenase kinase/phosphatase.” Susan P. Yates, Thomas E. Edwards, Cassie M. Bryan, Adam J. Stein, Wesley C. Van Voorhis, Peter J. Myler, Lance J. Stewart, Jimin Zheng, and Zongchao Jia. Biochemistry 2011, published online as an Accelerated Publication August 26, 2011.
Last Updated October 18, 2011
Last Reviewed October 18, 2011