Published September 25, 2023 | Version v1
Journal article Open

An interaction network in the polymerase active site is a prerequisite for Watson-Crick base paring in Pol g

Authors/Creators

  • 1. Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA
  • 2. Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, Texas 75080, USA
  • 3. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA
  • 4. Department of Chemistry and Biochemistry, Department of Physics, University of Texas at Dallas, Richardson, Texas 75080, USA
  • 5. Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA

Description

Pol gamma is essential for mitochondrial genome integrity. Mutations to the polymerase causes disruption to it's various functions. Mutations in the 853 site causes various neurological issues. Structural and computational analysis of the wild-type and the mutants show that the mutation inhibits the process of opening and closing of the polymerase necessary for nucleotide incorporation. Furthermore, the dNTP does not form Watson-Crick base pairing with the templating residue, which is necessary for the reaction to take place. Hence, we see that the single point mutation causes changes to the polymerase that inhibits its functionality.

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