You are here
Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis.
Title | Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | 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 |
Journal | BMC Struct Biol |
Volume | 11 |
Pagination | 39 |
Date Published | 2011 |
ISSN | 1472-6807 |
Keywords | Aldose-Ketose Isomerases, Amino Acid Sequence, Binding Sites, Catalytic Domain, Coccidioides, Crystallography, X-Ray, Iodides, Molecular Sequence Data, Protein Structure, Tertiary, Recombinant Proteins, Ribulosephosphates, Sequence Alignment, Substrate Specificity |
Abstract | BACKGROUND: Ribose-5-phosphate isomerase is an enzyme that catalyzes the interconversion of 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 and nucleotide and co-factor biogenesis. RESULTS: Although RpiB occurs predominantly in bacteria, here we report crystal structures of a putative RpiB from the pathogenic fungus Coccidioides immitis. A 1.9 Å resolution apo structure was solved by combined molecular replacement and single wavelength anomalous dispersion (SAD) phasing using a crystal soaked briefly in a solution containing a high concentration of iodide ions. RpiB from C. immitis contains modest sequence and high structural homology to other known RpiB structures. A 1.8 Å resolution phosphate-bound structure demonstrates phosphate recognition and charge stabilization by a single positively charged residue whereas other members of this family use up to five positively charged residues to contact the phosphate of ribose-5-phosphate. A 1.7 Å resolution structure was obtained in which the catalytic base of C. immitis RpiB, Cys76, appears to form a weakly covalent bond with the central carbon of malonic acid with a bond distance of 2.2 Å. This interaction may mimic that formed by the suicide inhibitor iodoacetic acid with RpiB. CONCLUSION: The C. immitis RpiB contains the same fold and similar features as other members of this class of enzymes such as a highly reactive active site cysteine residue, but utilizes a divergent phosphate recognition strategy and may recognize a different substrate altogether. |
DOI | 10.1186/1472-6807-11-39 |
Alternate Journal | BMC Struct. Biol. |
PubMed ID | 21995815 |