Dynamics of the thumb-finger regions in a GH11 xylanase Bacillus circulans: comparison between the Michaelis and covalent intermediate

The structure and dynamics of B. circulans β-1,4-xylanase (BCX) were comparatively studied utilizing molecular dynamics. Simulations of the free enzyme, non-covalently bound, and covalently bound xylobiose intermediate were conducted and post-dynamically studied to comprehend structural changes adopted during a reaction. Results showed that (a) covalent association of the substrate with the receptor induces a change in the structural conformation of the receptor; (b) the thumb region is highly flexible in the non-covalent complex compared to the covalent complex, drawing a conformational distinction between the two systems, a characteristic brought about by a more compact covalent complex structure in contrast to the non-covalent complex. This is most likely the result of a rigid covalent bond in addition to the hydrogen bond interactions between the substrate and receptor in the latter, (c) the distance between the thumb-finger residues Asp11-Pro116 is shortened upon substrate binding indicating that the flaps are drawn towards each other resulting in partial closing of the flaps. This study provides an invaluable contribution to the understanding of the dynamics of glycosidase enzymes which could largely contribute to the design of potent inhibitors targeting GH enzymes implicated in the orchestration of disease and disorders.