Key result
Molecular dynamics simulations of pol X/gapped DNA complexes showed that a conformational change from open to closed state in the G:G mispair is achieved only when the incoming nucleotide is syn.
Molecular dynamics simulations reveal that ASFV polymerase X accommodates G:G mispairs through a conformational change to a closed state when the incoming nucleotide is in the syn configuration.
No clinical implications yet; hypothesis-generating for syn-dependent G:G mispair accommodation by ASFV pol X.
The African Swine Fever Virus (ASFV) is an encapsulated deoxyvirus known to induce a lethal infection in domestic pigs. The double‐stranded DNA viral genome encodes a total of 151 proteins, including a minimal DNA repair system, with a repair polymerase, pol X, which catalyzes a single‐nucleotide filling in gapped DNA. Pol X, is the smallest naturally occurring DNA‐directed DNA polymerase described so far. It belongs to the X family of polymerases and shares sequence and structure similarity with human DNA polymerase β (pol β). However, where pol β is a moderate fidelity enzyme, pol X is much more error tolerant. The key feature of pol X is that the insertion rate of the G:G mispair is comparable to that of the four Watson‐Crick base pairs. Using molecular dynamics simulations (MD) we previously suggested an induced fit‐mechanism for pol X. The goal of this study is to understand at an atomic level, how pol X can accommodate mismatched base pairs more frequently compared to pol β. MD simulations of pol X/gapped DNA complexes in the presence of mismatched pairs were performed for 10.5 ns each using CHARMM package. Our results show that a conformational change, consistent with a transition from open to closed state, is achieved in the G:G mispair, only when the incoming nucleotide is in the syn configuration. Simulations results for other mismatched base pairs results will be presented and compared to the available kinetic data.
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Benítez et al. (2008) studied African Swine Fever Virus (ASFV). Molecular dynamics simulations of pol X/gapped DNA complexes was evaluated on Conformational change in the G:G mispair. Molecular dynamics simulations of pol X/gapped DNA complexes showed that a conformational change from open to closed state in the G:G mispair is achieved only when the incoming nucleotide is syn.
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