Presented here is a series of crystal structures solved by the Seattle Structural Genomics Center for Infectious Disease (SSGCID) of ribose-5-phosphate isomerase B, or RpiB, from the pathogenic fungus, Coccidioides immitis. This parasite, which resides in the soil in certain parts of the western hemisphere, causes coccidioidomycosis, also known as Valley Fever. The disease is difficult to diagnose as it causes masses which mimics a lung tumor.
Ribose-5-phosphate isomerase is an enzyme that catalyzes the conversion between ribose-5-phosphate and ribulose-5-phosphate. This family of enzymes naturally occurs in two distinct classes, RpiA and RpiB, which play, among others, an important role in the pentose phosphate pathway, which converts a type of glucose into other molecules. Although RpiB occurs predominantly in bacteria, the RpiB from this fungal pathogen contains high structural similarity to other known RpiB structures despite modest sequence similarity. The C. immitis structure of RpiB (PDB 3QD5), together with structures from Trypanosoma cruzi and Giardia lamblia (the latter of which was also solved by SSGCID, PDB 3S5P), are the only eukaryotic RpiB crystal structures currently available.
One of the solved structures, with phosphate-bound (PDB 3SDW, shown in the figure), demonstrates that the protein’s ability to recognize phosphate and stabilize charge is dependent upon a single positively charged residue of the protein, whereas other members of this family use up to five positively charged residues to contact the phosphate. Another structure was obtained which, together with the structure described above, reveals the presence of a highly reactive cysteine residue in the active site and provides insight into a possible structural mechanism for the inhibition of RpiB by the compound iodoacetate (PDB 3SGW). Combined, these structures provide insights into both the mode of action and possible mechanisms for inhibition for this protein.
These structures were published in the journal BMC Structural Biology. Reference: “Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis.” Edwards, T.E., Abramov, A.B., Smith, E.R., Baydo, R.O., Leonard, J.T., Leibly, D.J., Thompkins K.B., Clifton, M.C., Gardberg, A.S., Staker, B.L., Van Voorhis, W.C., Myler, P.J., and Stewart, L.J. BMC Structural Biol. (2011) 11:39. PMID: 21995815.