<p>Glucose-fructose oxidoreductase (GFOR) catalyses the formation of D-gluconolactone and D-glucitol from D-glucose and D-fructose. It hasone tightly-bound NADP(H) per enzyme subunit, it exists as a homotetramer,and is one of the pivotal proteins in the sorbitol-gluconate pathway. It istargeted to the periplasm of the Gram-negative cell envelope, and belongs tothe GFO/IDH/MOCA superfamily. First discovered in <taxon tax_id="542">Zymomonas mobilis</taxon>, homologues have also been found in <taxon tax_id="155892">Caulobacter crescentus</taxon> and <taxon tax_id="1299">Deinococcus radiodurans</taxon>.</p><p>GFOR is of great interest as its mechanism of secretion into the bacterialperiplasm differs from other precursor proteins of the Twin ArginineTranslocation (TAT) pathway [<cite idref="PUB00011610"/>]. Although it exhibits the consensus TAT signal motif (S/T-R-R-x-L-F-K) at its N terminus, unlike other TAT proteins that can be universally secreted across a number of Gram-negative microbes, GFOR is only translocated in Z. mobilis. However, replacing the Z. mobilis signal peptide with one from <taxon tax_id="562">Escherichia coli</taxon> restores this function. This observation has led to the suggestion that TAT-dependent precursors are optimally adapted only to their particular cognate secretion apparatus [<cite idref="PUB00011610"/>].</p><p>Recently, the crystal structure of Z. mobilis GFOR was resolved to 2.5A bymeans of X-ray crystallography. This revealed that the protein indeed exists as a homotetramer, and has 4 active sites. There are 2 distinct domains: a classical dinucleotide binding fold at the N terminus and a 9-stranded beta-sheet at the C terminus. NADP(H) is bound to the N terminus of the first alpha-helix.</p>