4irx

Publication Abstract from PubMed

The periplasmic binding protein (PBP) IbpA mediates the uptake of myo-inositol by the IatP-IatA ATP-binding cassette transmembrane transporter. We report a crystal structure of Caulobacter crescentus IbpA bound to myo-inositol at 1.45 A resolution. This constitutes the first structure of a PBP bound to inositol. IbpA adopts a type I PBP fold consisting of two alpha-beta lobes that surround a central hinge. A pocket positioned between the lobes contains the myo-inositol ligand, which binds with submicromolar affinity (0.76 +/- 0.08 muM). IbpA is homologous to ribose-binding proteins and binds D-ribose with low affinity (50.8 +/- 3.4 muM). On the basis of IbpA and ribose-binding protein structures, we have designed variants of IbpA with inverted binding specificity for myo-inositol and D-ribose. Five mutations in the ligand-binding pocket are sufficient to increase the affinity of IbpA for D-ribose by 10-fold while completely abolishing binding to myo-inositol. Replacement of ibpA with these mutant alleles unable to bind myo-inositol abolishes C. crescentus growth in medium containing myo-inositol as the sole carbon source. Neither deletion of ibpA nor replacement of ibpA with the high-affinity ribose binding allele affected C. crescentus growth on D-ribose as a carbon source, providing evidence that the IatP-IatA transporter is specific for myo-inositol. This study outlines the evolutionary relationship between ribose- and inositol-binding proteins and provides insight into the molecular basis upon which these two related, but functionally distinct, classes of periplasmic proteins specifically bind carbohydrate ligands.

myo-inositol and D-ribose ligand discrimination in an ABC periplasmic binding protein.,Herrou J, Crosson S J Bacteriol. 2013 May;195(10):2379-88. doi: 10.1128/JB.00116-13. Epub 2013 Mar, 15. PMID:23504019^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.