Journal Article FZJ-2016-05997

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A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases

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2016
American Chemical Society Washington, DC

Journal of the American Chemical Society 138(44), 14592 - 14598 () [10.1021/jacs.6b05475]

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Abstract: 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.

Classification:

Contributing Institute(s):
  1. Computational Biomedicine (IAS-5)
  2. Computational Biomedicine (INM-9)
Research Program(s):
  1. 899 - ohne Topic (POF3-899) (POF3-899)

Appears in the scientific report 2016
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Medline ; OpenAccess ; BIOSIS Previews ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Free to read ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2016-11-11, last modified 2024-06-25