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RpiB from Coccidioides immitis

Researchers from the Seattle Structural Genomics Center for Infectious Disease (SSGCID) have determined a series of crystal structures of ribose-5-phosphate isomerase B, or RpiB, from the pathogenic fungus, Coccidioides immitis. This fungus resides in the soil and can be breathed in by humans, causing coccidioidomycosis, or Valley Fever. The disease typically occurs in the desert regions of the southwestern United States and in Central and South America. It can be difficult to diagnose as it causes masses which mimic 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 an important role in the pentose phosphate pathway, a process which converts a type of glucose into other molecules. The structure of RpiB from C. immititis is similar to other known RpiB structures. The C. immitis structure of RpiB (PDB 3QD5), and structures from Trypanosoma cruzi and Giardia lamblia, which which was also solved by SSGCID, PDB 3S5P, are the only eukaryotic RpiB crystal structures currently available.

One of the solved structures of RpiB from C. immititis, with phosphate-bound (PDB 3SDW, shown in the figure below), 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.

SSGCID researchers also determined another structure of this enzyme bound to malonic acid 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 improve scientific understanding of RpiB’s mode of action and therefore possible mechanisms for interrupting the pentose phosphate pathway via protein inhibition.

Publication

Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis. Edwards TE, Abramov AB, Smith ER, Baydo RO, Leonard JT, Leibly DJ, Thompkins KB, Clifton MC, Gardberg AS, Staker BL, Van Voorhis WC, Myler PJ, Stewart LJ. BMC Structural Biol. (2011) 11:39. PMID: 21995815.

 

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Last Updated June 06, 2012

Last Reviewed June 06, 2012