August 31, 2016 Journal article Closed Access

Marco De Vivo; Marco De Vivo; Emiliano Ippoliti; Vito Genna; Vito Genna; Paolo Carloni; Pietro Vidossich

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{
  "@context": "https://schema.org/", 
  "@id": "https://doi.org/10.1021/jacs.6b05475", 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "name": "Marco De Vivo"
    }, 
    {
      "@type": "Person", 
      "name": "Marco De Vivo"
    }, 
    {
      "@type": "Person", 
      "name": "Emiliano Ippoliti"
    }, 
    {
      "@type": "Person", 
      "name": "Vito Genna"
    }, 
    {
      "@type": "Person", 
      "name": "Vito Genna"
    }, 
    {
      "@type": "Person", 
      "name": "Paolo Carloni"
    }, 
    {
      "@type": "Person", 
      "name": "Pietro Vidossich"
    }
  ], 
  "datePublished": "2016-08-31", 
  "description": "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\u2032-OH and \u03b2-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-\u03b7, 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.", 
  "headline": "A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases", 
  "identifier": "https://doi.org/10.1021/jacs.6b05475", 
  "image": "https://zenodo.org/static/img/logos/zenodo-gradient-round.svg", 
  "inLanguage": {
    "@type": "Language", 
    "alternateName": "eng", 
    "name": "English"
  }, 
  "keywords": [
    "Colloid and Surface Chemistry", 
    "Biochemistry", 
    "General Chemistry", 
    "Catalysis"
  ], 
  "license": "", 
  "name": "A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases", 
  "url": "https://www.openaccessrepository.it/record/91731"
}