This title appears in the Scientific Report :
2016
Please use the identifier:
http://dx.doi.org/10.1021/jacs.6b05475 in citations.
Please use the identifier: http://hdl.handle.net/2128/12752 in citations.
A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases
A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases
The 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-phosphat...
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Personal Name(s): | Genna, Vito |
---|---|
Vidossich, Pietro / Ippoliti, Emiliano / Carloni, Paolo (Corresponding author) / Vivo, Marco De (Corresponding author) | |
Contributing Institute: |
Computational Biomedicine; INM-9 Computational Biomedicine; IAS-5 |
Published in: | Journal of the American Chemical Society, 138 (2016) 44, S. 14592 - 14598 |
Imprint: |
Washington, DC
American Chemical Society
2016
|
PubMed ID: |
27530537 |
DOI: |
10.1021/jacs.6b05475 |
Document Type: |
Journal Article |
Research Program: |
ohne Topic |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/12752 in citations.
The 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. |