Ligand-induced fit affects binding modes and provokes changes in crystal packing of aldose reductase

► Structural and energetic consequences of the mutational exchange of a residue in the specificity pocket of aldose reductase. ► Study by high resolution crystallography and isothermal titration calorimetry. ► Three carboxylate-type inhibitors investigated, one with specificity pocket in closed, two in opened state. ► Inhibitor induced-fit adaptations provoke the transition into another crystal form. ► New crystal form avoids packing contacts to the crucially affected residues.