Figure 3
ATP hydrolysis at AS1 activates hydrolysis at AS2. (a) Evolution of the distance between the oxygen atom of the catalytic water in AS2 and the ε-amino group of the Smc1A-K1120 residue (distance K1120-NZ - wat-O) prior (red) and after (cyan) ATP hydrolysis at AS1. (b) AS2 activation and QM region description. The atoms in the QM region of the QM/MM MD simulations of AS2 are represented by coloured ball and sticks. Part of the MM region of the ATP is shown (white ball and sticks). The positions of the catalytic water (wat), Smc3-K38, Smc3-E1144 and Smc1A-K1120 residues, and the ATP molecule are indicated for both inactive (AS1-ATP/AS2-ATP, red line) and active (AS1-ADP/AS2-ATP, cyan line) AS2 configurations. The distance between the catalytic water and ε-amino group of the Smc1A-K1120 residue is indicated by a black arrow. The reaction coordinate (RC) is indicated by a purple arrow. (c) Free-energy (kcal mol−1) profiles generated via QM/MM MD simulations of AS2 in both inactive (AS1-ATP/AS2-ATP, red line) and active (AS1-ADP/AS2-ATP, cyan line) configurations. The X-axis represents the reaction coordinate RC (bond to be formed): the distance (in Å) between the oxygen atom of the catalytic water and the phosphorous atom of the ATP molecule γ-phosphate group (distance ATP-PG - wat-O). The substrate (S), transition state (TS) and product (P).
