Network of Dynamically Important Residues in the Open/Closed Transition in Polymerases Is Strongly Conserved

Summary The open/closed transition in polymerases is a crucial event in DNA replication and transcription. We hypothesize that the residues that transmit the signal for the open/closed transition are also strongly conserved. To identify the dynamically relevant residues, we use an elastic network model of polymerases and probe the residue-specific response to a local perturbation. In a variety of DNA/RNA polymerases, a network of residues spanning the fingers and palm domains is involved in the open/closed transition. The similarity in the network of residues responsible for large-scale domain movements supports the notion of a common induced-fit mechanism in the polymerase families for the formation of a closed ternary complex. Multiple sequence alignment shows that many of these residues are also strongly conserved. Residues with the largest sensitivity to local perturbations include those that are not so obviously involved in the polymerase catalysis. Our results suggest that mutations of the mechanical "hot spots" can compromise the efficiency of the enzyme.