Figure 3.

Active-site and dTTP-binding pocket coordination and rearrangement in pol μ. (a) Representative active-site conformation of pol μ from simulation I. Bold dashed lines indicate coordination around Mg²⁺; thin dashed lines indicate hydrogen bonds between water molecules and the DNA/dTTP. Mg²⁺(A), catalytic ion; Mg²⁺(B), nucleotide-binding ion. (b) Comparison of His³²⁹-Asp³³⁰ in pol μ in simulations I (red, with dTTP) and II (green, without dTTP). Bold dashed lines indicate coordination around Mg²⁺, black thin dashed lines indicate hydrogen bonds formed in simulation I, and blue thin dashed lines indicate hydrogen bonds formed in simulation II. (c) The location of the dTTP-binding pocket in pol μ (red, Gln⁴⁴⁰ and Glu⁴⁴³ in simulation I; green, Gln⁴⁴⁰ and Glu⁴⁴³ in simulation II; blue, A5 and T17 in DNA). Dashed lines indicate the distances used in cluster analysis (Fig. 3f). (d) Comparison of the dTTP-binding pocket of pol μ (left) and pol λ (right). Structures with dTTP are marked red (simulation I of pol μ, and ternary crystal structure of pol λ); structures without dTTP are marked green (simulation II of pol μ, and binary crystal structure of pol λ). Dashed lines indicate hydrogen bonds. The names of residues controlling the accommodating process are shown in red. (e) Comparison of active-site conformation of pol μ in simulations I (red and blue, with dTTP) and II (green, without dTTP). Asp³³⁰ in simulation I is marked blue. (f) Cluster analysis of Gln⁴⁴⁰ (left) and Glu⁴⁴³ (right) in simulations I (red) and II (black) based on dihedral angles (CA-CB-CG-CD) and distances to the DNA (Gln⁴⁴⁰:NE2-T17:C5M or Glu⁴⁴³:CD-A5:C2).