Journal article Closed Access
Marco De Vivo; Marco De Vivo; Emiliano Ippoliti; Vito Genna; Vito Genna; Paolo Carloni; Pietro Vidossich
<?xml version='1.0' encoding='utf-8'?> <resource xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://datacite.org/schema/kernel-4" xsi:schemaLocation="http://datacite.org/schema/kernel-4 http://schema.datacite.org/meta/kernel-4.1/metadata.xsd"> <identifier identifierType="URL">https://www.openaccessrepository.it/record/91731</identifier> <creators> <creator> <creatorName>Marco De Vivo</creatorName> </creator> <creator> <creatorName>Marco De Vivo</creatorName> </creator> <creator> <creatorName>Emiliano Ippoliti</creatorName> </creator> <creator> <creatorName>Vito Genna</creatorName> </creator> <creator> <creatorName>Vito Genna</creatorName> </creator> <creator> <creatorName>Paolo Carloni</creatorName> </creator> <creator> <creatorName>Pietro Vidossich</creatorName> </creator> </creators> <titles> <title>A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases</title> </titles> <publisher>INFN Open Access Repository</publisher> <publicationYear>2016</publicationYear> <subjects> <subject>Colloid and Surface Chemistry</subject> <subject>Biochemistry</subject> <subject>General Chemistry</subject> <subject>Catalysis</subject> </subjects> <dates> <date dateType="Issued">2016-08-31</date> </dates> <language>en</language> <resourceType resourceTypeGeneral="Text">Journal article</resourceType> <alternateIdentifiers> <alternateIdentifier alternateIdentifierType="url">https://www.openaccessrepository.it/record/91731</alternateIdentifier> </alternateIdentifiers> <relatedIdentifiers> <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1021/jacs.6b05475</relatedIdentifier> <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://www.openaccessrepository.it/communities/itmirror</relatedIdentifier> </relatedIdentifiers> <rightsList> <rights rightsURI="info:eu-repo/semantics/closedAccess">Closed Access</rights> </rightsList> <descriptions> <description descriptionType="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.</description> </descriptions> </resource>
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