Crystal structure of glucose dehydrogenase from Bacillus megaterium IWG3 at 1.7 angstrom resolution

The crystal structure of glucose dehydrogenase (GlcDH) from Bacillus megate rium IWG3 has been determined to an R-factor of 17.9% at 1.7 Angstrom resol ution. The enzyme consists of four identical subunits, which are similar to those of other short-chain reductases/dehydrogenases (SDRs) in their overa ll folding and subunit architecture, although cofactor binding sites and su bunit interactions differ. Whereas a pair of basic residues is well conserv ed among NADP(+)-preferring SDRs, only Arg39 was found around the adenine r ibose moiety of GlcDH. This suggests that one basic amino acid is enough to determine the coenzyme specificity. The four subunits are interrelated by three mutually perpendicular diad axes (P, Q, and R). While subunit interac tions through the P-axis for GlcDH are not so different from those of the o ther SDRs, those through the Q-axis differ significantly. GlcDH was found t o have weaker hydrophobic interactions in the Q-interface. Moreover, GlcDH lacks the salt bridge that stabilizes the subunit interaction in the Q-inte rface in the other SDRs. Hydrogen bonds between Q-axis related subunits are also less common than in the other SDRs. The GlcDH tetramer dissociates in to inactive monomers at pH 9.0, which can be attributed mainly to the weakn ess of the Q-axis interface.