The mechanism of glucose isomerization to fructose catalyzed by Lewis acidic Sn sites in the framework of MOR, BEA, MFI and MWW zeolites was investigated by periodic DFT calculations. The main focus was on the influence of the nature of the active site and the zeolite topology on the rate-controlling hydride shift step. A general finding is that the Sn-catalyzed isomerization of glucose is strongly promoted by proximate hydroxyl groups. These hydroxyl groups can derive from co-adsorbed water molecules or internal silanols. The cooperative action of such proton donors with the Lewis acidic Sn sites results in more effective compensation of the negative charge developing on the O1 atom of glucose during the rate-controlling hydride shift reaction step. The variation in the shape of the micropores with a zeolite topology affects the mode and strength of carbohydrate adsorption, which is dominated by van der Waals forces. Their influence on the intrinsic reactivity of intrazeolite Sn sites is small. We propose that higher glucose adsorption energy in the narrower micropores of 10-membered ring zeolites (e.g., Sn-MFI and Sn-MWW) adversely affects the intrachannel diffusion compared to that in the zeolites with larger pores. The high catalytic performance of Sn-MWW towards glucose transformation is due to the lower barrier for the hydride shift step resulting from the presence of a relatively strong acidic bridging silanol group next to the Lewis acidic Sn site.