The structure of a novel membrane-associated 6-phosphogluconate dehydrogenase fromGluconacetobacter diazotrophicus(Gd6PGD) reveals a subfamily of short-chain 6PGDs

The enzyme 6-phosphogluconate dehydrogenase catalyzes the conversion of 6-phosphogluconate to ribulose-5-phosphate. It represents an important reaction in the oxidative pentose phosphate pathway, producing a ribose precursor essential for nucleotide and nucleic acid synthesis. We succeeded, for the first time, to determine the three-dimensional structure of this enzyme from an acetic acid bacterium,Gluconacetobacter diazotrophicus(Gd6PGD). ActiveGd6PGD, a homodimer (70 kDa), was present in both the soluble and the membrane fractions of the nitrogen-fixing microorganism. TheGd6PGD belongs to the newly described subfamily of short-chain (333 AA) 6PGDs, compared to the long-chain subfamily (480 AA; e.g.,Ovis aries, Homo sapiens). The shorter amino acid sequence inGd6PGD induces the exposition of hydrophobic residues in the C-terminal domain. This distinct structural feature is key for the protein to associate with the membrane. Furthermore, in terms of function, the short-chain 6PGD seems to prefer NAD(+)over NADP(+), delivering NADH to the membrane-bound NADH dehydrogenase of the microorganisms required by the terminal oxidases to reduce dioxygen to water for energy conservation. Enzyme . Database Structural data are available in PDB database under the accession number .