Aldose reductase (ALR2; EC 1.1.1.21) is a member of the aldoketo reductase superfamily and it catalyzes the NADPH-dependent reduction of aldeydes to their corresponding alcohols. It is implicated in the polyol pathway and in diabetic complication. The crystal structure of native aldose reductase has been determined to a resolution of 0.82 Å with a final R = 9.50 and R free = 10.90 and a mean coordinate error for the fully occupied sites of the protein of 0.011 Å (from fully matrix inversion). The structure contains a large number of multiple conformations: 78 out of 316 residues were modeled in two conformations. The overall structure folds into an eight-stranded / barrel with the active site located at the C-terminal end of the barrel and the NADP +-binding site near the hydrophobic binding pocket [1]. The cofactor is held in place by the so-called 'safety-belt' (a loop between residue 216 and 227 of the canonical / barrel) [2]. The active site of the structure contains a citrate molecule in two conformations. One of the conformations stabilizes the closed position of the safety-belt, whereby the other permits the safety-belt to open. Due to the high resolution, the partially opened conformation of the safety-belt can be observed in the electron density.

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The first X-ray crystallographic electron density map of a ribosomal subunit showing recognizable molecular features was of the Haloarcula marismortui 50S published at 9 Å resolution (Ban et al., 1998) and showed rods of density corresponding to duplex RNA crisscrossing the subunit. Extension of phasing to 5 Å resolution allowed the fitting of known protein and RNA structures but not extensive tracing of the RNA backbone (Ban et al., 1999). The resolution of an experimentally phased electron density map of the Haloarcula marismortui 50 S ribosomal subunit has now been extended to 2.7 Å resolution using heavy atom derivative data to 3.2 Å resolution and density modification procedures. A complete model of the approximately 3,000 nucleotides of the 23S and 5S RNAs has been constructed and partially refined against the experimental diffraction amplitudes and experimental phases to give a free R-factor of 0.35 at 2.7 Å resolution. Positioning of the substrate analogue CCdA-puromycin into this model shows that the ribosome is a ribozyme, since there is no protein electron density closer than about 18 Å from the bond being synthesized. * These authors contributed equally.Ban N., Freeborn B., Nissen P., Penczek P., Grassuci R.A., Sweet R., Frank J., Moore P.B. and Steitz T.A. "A 9 Å resolution X-ray crystallographic map of the large ribosomal subunit". Cell, (1998), 93: 1105 -1115. Ban N., Nissen P., Hansen J., Capel M., Moore P.B. and Steitz T.A. "Placement of protein and RNA structures into a 5 Å resolution map of the 50S ribosomal subunit". Nature, (1999), 400: 841 -847. s8a.m3.o2