Structural features of archaeal β-phosphoglucomutase from hyperthermophilic Pyrococcus sp. ST04

β-Phosphoglucomutase (β-PGM) catalyzes the conversion of β-glucose-1-phosphate (β-G1P) to glucose-6-phosphate (G6P). Upon binding to the substrate, β-PGM adopts a conformational change of cap domain over the core domain with concomitant closure of the active sites located at the domain interface. Recently we have identified a novel β-PGM from Pyrococcus sp. ST04 (PsPGM) that is highly thermostable, with an optimal temperature of 95℃. The crystal structure of PsPGM shows two domains: the core domain with a typical β/α barrel-fold of haloacid dehalogenase (HAD) family, and the cap domain with α-helical bundles. The core domain contains the active site with the conserved Asp7 and cofactor Mg2+, exposing the catalytic residue to the surface. Unlike bacterial β-PGMs, the cap domain of PsPGM exists in a significantly tilted, half-closed conformation, which positions Lys82 in close proximity to the substrate binding in the absence of ligand. This unique configuration of the cap domain distinguishes this archaic enzyme from typical bacterial β-PGMs and provides a molecular basis for its enzymatic characteristics at high temperature.