The structure and domain organization of Escherichia coli isocitrate lyase

Enzymes of the glyoxylate-bypass pathway are potential targets for the cont rol of many human diseases caused by such pathogens as Mycobacteria and Lei shmania. Isocitrate lyase catalyses the first committed step in this pathwa y and the structure of this tetrameric enzyme from Escherichia coli has bee n determined at 2.1 Angstrom resolution. E. coli isocitrate lyase, like the enzyme from other prokaryotes, is located in the cytoplasm, whereas in pla nts, protozoa, algae and fungi this enzyme is found localized in glyoxysome s. Comparison of the structure of the prokaryotic isocitrate lyase with tha t from the eukaryote Aspergillus nidulans reveals a different domain struct ure following the deletion of approximately 100 residues from the larger eu karyotic enzyme. Despite this, the active sites of the prokaryotic and euka ryotic enzymes are very closely related, including the apparent disorder of two equivalent segments of the protein that are known to be involved in a conformational change as part of the enzyme's catalytic cycle.