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'?> <record xmlns="http://www.loc.gov/MARC21/slim"> <leader>00000nam##2200000uu#4500</leader> <datafield tag="041" ind1=" " ind2=" "> <subfield code="a">eng</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Marco De Vivo</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Emiliano Ippoliti</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Vito Genna</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Vito Genna</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Paolo Carloni</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Pietro Vidossich</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">publication</subfield> <subfield code="b">article</subfield> </datafield> <datafield tag="542" ind1=" " ind2=" "> <subfield code="l">closed</subfield> </datafield> <controlfield tag="005">20230925015016.0</controlfield> <datafield tag="024" ind1=" " ind2=" "> <subfield code="a">10.1021/jacs.6b05475</subfield> <subfield code="2">doi</subfield> </datafield> <datafield tag="520" ind1=" " ind2=" "> <subfield code="a">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.</subfield> </datafield> <datafield tag="260" ind1=" " ind2=" "> <subfield code="c">2016-08-31</subfield> </datafield> <datafield tag="100" ind1=" " ind2=" "> <subfield code="a">Marco De Vivo</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">Colloid and Surface Chemistry</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">Biochemistry</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">General Chemistry</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">Catalysis</subfield> </datafield> <datafield tag="650" ind1="1" ind2="7"> <subfield code="a">cc-by</subfield> <subfield code="2">opendefinition.org</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">user-itmirror</subfield> </datafield> <controlfield tag="001">91731</controlfield> <datafield tag="245" ind1=" " ind2=" "> <subfield code="a">A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases</subfield> </datafield> <datafield tag="540" ind1=" " ind2=" "> <subfield code="a">Other (Open)</subfield> </datafield> </record>
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