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Figure 2
Categories of conformational change that could accompany Schiff-base formation within an active site. The nucleophilic approach of the lysine N atom to a substrate carbonyl is predicted to follow an obtuse αBD (see Fig. 1[link]). (a) Pre-nucleophilic attack state. The substrate forms an initial interaction with the enzyme that positions its carbonyl at an appropriate αBD relative to the lysine N atom. For the N atom to assume an obtuse αBD but ultimately represent a component of the Schiff base, it follows that >90° of angular rotation must occur in the intervening bond formation. Three categories of positional/conformational change could occur individually or in combination to achieve this rotation. (b) Rigid enzyme, rigid substrate. In this case, the conformations of main/side chains of the enzyme do not change from the pre-nucleophilic attack state positions, but the overall position of the substrate changes via gross rotation toward the lysine N atom, without significant change to internal substrate dihedral angles. (c) Flexible enzyme, rigid substrate. The position and internal dihedrals of the substrate do not change from their pre-nucleophilic attack state values, but significant protein conformational change results in movement of the lysine N atom toward the plane of the substrate carbonyl. (d) Rigid enzyme, flexible substrate. The conformation of the enzyme and the gross position of the substrate do not change, but a significant substrate conformational change (change in internal dihedrals) results in rotation of the plane of the substrate carbonyl towards the lysine N atom. Within the schematic representation, the substructures of the carbonyl substrate, R1C(O)R2, are represented by the maroon ribbon, with internal conformational change indicated by a twist in the ribbon. The active site with its reactive lysine is represented within the dark blue body and ledge.

Journal logoBIOLOGICAL
CRYSTALLOGRAPHY
ISSN: 1399-0047
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