Amino acid changes coded by bacteriophage T4 DNA polymerase mutator mutants. Relating structure to function.

Abstract:

Previous studies on the selection of bacteriophage T4 mutator mutants have been extended and a method to regulate the mutator activity of DNA polymerase mutator strains has been developed. The nucleotide changes of 17 bacteriophage T4 DNA polymerase mutations that confer a mutator phenotype and the nucleotide substitutions of several other T4 DNA polymerase mutations have been determined. The most striking observation is that the distribution of DNA polymerase mutator mutations is not random; almost all mutator mutations are located in the N-terminal half of the DNA polymerase. It has been shown that the T4 DNA polymerase shares several regions of homology at the protein sequence level with DNA polymerases of herpes, adeno and pox viruses. From studies of bacteriophage T4 and herpes DNA polymerase mutants, and from analyses of similar protein sequences from several organisms, we conclude that DNA polymerase synthetic activities are located in the C-terminal half of the DNA polymerase and that exonucleolytic activity is located nearer the N terminus.

Polymerases:

Topics:

Mutational Analysis, Structure and Structure/Function, Fidelity, Nucleotide Incorporation, Exonuclease Activity, Methods, Alignments

Status:

new topics/pols set partial results complete validated

Results:

Polymerase Reference Property Result Context
T4 Q592S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.01 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q592K Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 G82D Reha-Krantz LJ1988 Nucleotide Substitution Rate 45 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 Y317C Reha-Krantz LJ1988 Nucleotide Substitution Rate 410 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 L340P Reha-Krantz LJ1988 Nucleotide Substitution Rate 210 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 S345P Reha-Krantz LJ1988 Nucleotide Substitution Rate 25 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 G694S Reha-Krantz LJ1988 Nucleotide Substitution Rate 3 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 L309P Reha-Krantz LJ1988 Nucleotide Substitution Rate 716 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 V325A Reha-Krantz LJ1988 Nucleotide Substitution Rate 105 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 N456TE881K Reha-Krantz LJ1988 Nucleotide Substitution Rate 320 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 Q478RA488V Reha-Krantz LJ1988 Nucleotide Substitution Rate 103 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 W213Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.15 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W213S Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W202Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W202Q Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W202S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.2 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q386S Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 errors/bp Technique: T4 rII 199oc reversion assay
T4 Q386K Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q386Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.2 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q430Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q430K Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q430S Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W458S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.05 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W458Q Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W458Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.2 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W458K Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.2 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W482S Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W482Q Reha-Krantz LJ1988 Nucleotide Substitution Rate 6 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W482Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W482K Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q730S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.001 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q730Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q730K Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 D131N Reha-Krantz LJ1988 Nucleotide Substitution Rate 45 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 D131G Reha-Krantz LJ1988 Nucleotide Substitution Rate 125 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 G255S Reha-Krantz LJ1988 Nucleotide Substitution Rate 328 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 G298D Reha-Krantz LJ1988 Nucleotide Substitution Rate 174 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 G304D Reha-Krantz LJ1988 Nucleotide Substitution Rate 154 Mutation frequency (relative to WT) Technique: ac forward mutational assay
T4 W593S Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W593Q Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W593Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 7 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W593K Reha-Krantz LJ1988 Nucleotide Substitution Rate 1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W844S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.002 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 W844Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.1 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q731S Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.004 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q731Y Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.01 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay
T4 Q731K Reha-Krantz LJ1988 Nucleotide Substitution Rate 0.01 Mutation frequency (relative to WT) Technique: T4 rII 199oc reversion assay

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