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Publication Abstract from PubMed

Ribose-1,5-bisphosphate isomerase (R15Pi) is a novel enzyme recently identified as a member of an AMP metabolic pathway in archaea. The enzyme converts D-ribose 1,5-bisphosphate (R15P) into ribulose 1,5-bisphosphate (RuBP), providing the substrate for archaeal ribulose-1,5-bisphosphate carboxylase/oxygenases. We here report the crystal structures of R15Pi from Thermococcus kodakarensis KOD1 (Tk-R15Pi) with and without its substrate or product. Tk-R15Pi is a hexameric enzyme formed by the trimerization of dimer units. Biochemical analyses show that Tk-R15Pi only accepts the alpha-anomer of R15P and that Cys133 and Asp202 residues are essential for RuBP production. Comparison of the determined structures reveals that the unliganded and product-binding structures are in an open form, whereas the substrate-binding structure adopts a closed form, indicating domain movement upon substrate binding. The conformational change to the closed form optimizes active-site configuration and also isolates the active site from the solvent, which may allow deprotonation of Cys133 and protonation of Asp202 to occur. The structural features of the substrate-binding form and biochemical evidence lead us to propose that the isomerase reaction proceeds via a cis-phosphoenolate intermediate.

Dynamic, ligand-dependent conformational change triggers the reaction of ribose-1,5-bisphosphate isomerase from Thermococcus kodakarensis KOD1.,Nakamura A, Fujihashi M, Aono R, Sato T, Nishiba Y, Yoshida S, Yano A, Atomi H, Imanaka T, Miki K J Biol Chem. 2012 Apr 17. PMID:22511789^[1]

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