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The activity of all of the mutated enzymes with non-specific substrates indicates that the substrate binding pocket is altered and has become flexible toward other substrates after mutation.
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To answer this question we developed a panel of peptides designed so that amino acids interacting with the p6 and p9 predicted MHC binding pockets were altered.
It is possible that the shorter side chain of leucine causes distal conformational changes that re-position D681, R717 and L828 such that the channel leading to the binding pocket is enlarged or the dynamics of substrate efflux is altered.
Moreover, a new binding pocket is also explored.
The binding pocket is indicated as an exclusion surface.
The positively charged binding pocket is not big enough for ANP binding.
Replacement of water from the uncomplexed binding pocket is assumed to be entropically favorable.
Docked ligand conformation, is presented with sticks and the binding pocket is shown as surface.
The negatively charged binding pocket is not big enough for ATP (Fig. 2B).
The volume of the binding pocket is 495 Å.
Four binding pockets are marked as A, B, C, and D. Another binding pocket is marked as LBD.
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