title: Arabinose 5-phosphate covalently inhibits transaldolase.
abstract: Arabinose 5-phosphate (A5P) is the aldopentose version of the ketohexose fructose 6-phosphate (F6P), having identical stereochemistry but lacking atoms corresponding to the 1-carbon and 1-hydroxyl. Despite structural similarity and conservation of the reactive portion of F6P, F6P acts as a substrate whereas A5P is reported to be an inhibitor of transaldolase. To address the lack of A5P reactivity we determined a crystal structure of the Francisella tularensis transaldolase in complex with A5P. This structure reveals that like F6P, A5P forms a covalent Schiff base with active site Lys135. Unlike F6P, A5P binding fails to displace an ordered active site water molecule. Retaining this water necessitates conformational changes at the A5P-protein linkage that possibly hinder reactivity. The findings presented here show the basis of A5P inhibition and suggest an unusual mechanism of competitive, reversible-covalent transaldolase regulation.
authors: Center for Structural Genomics of Infectious Diseases, Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors: Samuel H
authors: SH
authors: Light
authors: Wayne F
authors: WF
authors: Anderson
mesh_terms: D005604:Francisella tularensis / Q000201:enzymology; D005636:Fructosephosphates / Q000737:chemistry; D008958:Models, Molecular; D010428:Pentosephosphates / Q000378:metabolism*; D011487:Protein Conformation; D012545:Schiff Bases / Q000737:chemistry; D013379:Substrate Specificity; D014153:Transaldolase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D005636:Fructosephosphates; D010428:Pentosephosphates; D012545:Schiff Bases; C028055:arabinose 5-phosphate; C027618:fructose-6-phosphate; D014153:Transaldolase