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A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases
Version 2 2016-11-28, 17:49
Version 1 2016-08-31, 20:14
journal contribution
posted on 2016-11-09, 00:00 authored by Vito Genna, Pietro Vidossich, Emiliano Ippoliti, Paolo Carloni, Marco De VivoThe enzymatic polymerization of DNA and RNA
is the basis for genetic inheritance for all living organisms. It
is catalyzed by the DNA/RNA polymerase (Pol) superfamily.
Here, bioinformatics analysis reveals that the incoming nucleotide
substrate always forms an H-bond between its 3′-OH and
β-phosphate moieties upon formation of the Michaelis complex.
This previously unrecognized H-bond implies a novel self-activated
mechanism (SAM), which synergistically connects the in situ nucleophile
formation with subsequent nucleotide addition
and, importantly, nucleic acid translocation. Thus, SAM allows an
elegant and efficient closed-loop sequence of chemical
and physical steps for Pol catalysis. This is markedly different from
previous mechanistic hypotheses. Our proposed mechanism is corroborated
via ab initio QM/MM simulations on a specific Pol, the human DNA polymerase-η,
an enzyme involved in repairing damaged DNA. The structural conservation
of DNA and RNA Pols supports the possible extension of SAM to Pol
enzymes from the three domains of life.
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- Biophysics
- Biochemistry
- Physical Sciences not elsewhere classified
- Microbiology
- Cell Biology
- Genetics
- Molecular Biology
- Environmental Sciences not elsewhere classified
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- Developmental Biology
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