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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{
  "DOI": "10.1021/jacs.6b05475", 
  "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\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.", 
  "author": [
    {
      "family": "Marco De Vivo"
    }, 
    {
      "family": "Marco De Vivo"
    }, 
    {
      "family": "Emiliano Ippoliti"
    }, 
    {
      "family": "Vito Genna"
    }, 
    {
      "family": "Vito Genna"
    }, 
    {
      "family": "Paolo Carloni"
    }, 
    {
      "family": "Pietro Vidossich"
    }
  ], 
  "id": "91731", 
  "issued": {
    "date-parts": [
      [
        2016, 
        8, 
        31
      ]
    ]
  }, 
  "language": "eng", 
  "note": "", 
  "title": "A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases", 
  "type": "article-journal"
}