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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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Marco De Vivo</dc:creator>
  <dc:creator>Marco De Vivo</dc:creator>
  <dc:creator>Emiliano Ippoliti</dc:creator>
  <dc:creator>Vito Genna</dc:creator>
  <dc:creator>Vito Genna</dc:creator>
  <dc:creator>Paolo Carloni</dc:creator>
  <dc:creator>Pietro Vidossich</dc:creator>
  <dc:date>2016-08-31</dc:date>
  <dc: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′-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.</dc:description>
  <dc:identifier>https://www.openaccessrepository.it/record/91731</dc:identifier>
  <dc:identifier>10.1021/jacs.6b05475</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>url:https://www.openaccessrepository.it/communities/itmirror</dc:relation>
  <dc:rights>info:eu-repo/semantics/closedAccess</dc:rights>
  <dc:subject>Colloid and Surface Chemistry</dc:subject>
  <dc:subject>Biochemistry</dc:subject>
  <dc:subject>General Chemistry</dc:subject>
  <dc:subject>Catalysis</dc:subject>
  <dc:title>A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>