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DNA polymerase β catalytic efficiency mirrors the Asn279–dCTP H‐bonding strength
Author(s) -
Martínek Václav,
Bren Urban,
Goodman Myron F.,
Warshel Arieh,
Florián Jan
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.01.042
Subject(s) - dna polymerase , dna polymerase beta , polymerase , chemistry , dna , mutant , ternary operation , dna clamp , microbiology and biotechnology , biophysics , crystallography , biology , biochemistry , polymerase chain reaction , gene , dna repair , reverse transcriptase , computer science , base excision repair , programming language
Ternary complexes of wild type or mutant form of human DNA polymerase β (pol β) bound to DNA and dCTP substrates were studied by molecular dynamics (MD) simulations. The occurrences of contact configurations (CC) of structurally important atom pairs were sampled along the MD trajectories, and converted into free‐energy differences, Δ G CC . Δ G CC values were correlated with the experimental binding and catalytic free energies for the wild type pol β and its Arg183Ala, Tyr271Ala, Asp276Val, Lys280Gly, Arg283Ala, and Glu295Ala mutants. The correlation coefficients show that the strength of the H‐bond between dCTP and Asn279 is a strong predictor of the mutation‐induced changes in the catalytic efficiency of pol β. This finding is consistent with the view that enzyme preorganization plays a major role in controlling DNA polymerase specific activity.