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@ARTICLE{Genna:844312,
      author       = {Genna, Vito and Carloni, Paolo and De Vivo, Marco},
      title        = {{A} {S}trategically {L}ocated {A}rg/{L}ys {R}esidue
                      {P}romotes {C}orrect {B}ase {P}aring {D}uring {N}ucleic
                      {A}cid {B}iosynthesis in {P}olymerases},
      journal      = {Journal of the American Chemical Society},
      volume       = {140},
      number       = {9},
      issn         = {1520-5126},
      address      = {Washington, DC},
      publisher    = {American Chemical Society},
      reportid     = {FZJ-2018-01745},
      pages        = {3312 - 3321},
      year         = {2018},
      abstract     = {Polymerases (Pols) synthesize the double-stranded nucleic
                      acids in the Watson–Crick (W–C) conformation, which is
                      critical for DNA and RNA functioning. Yet, the molecular
                      basis to catalyze the W–C base pairing during Pol-mediated
                      nucleic acids biosynthesis remains unclear. Here, through
                      bioinformatics analyses on a large data set of Pol/DNA
                      structures, we first describe the conserved presence of one
                      positively charged residue (Lys or Arg), which is similarly
                      located near the enzymatic two-metal active site, always
                      interacting directly with the incoming substrate (d)NTP.
                      Incidentally, we noted that some Pol/DNA structures showing
                      the alternative Hoogsteen base pairing were often solved
                      with this specific residue either mutated, displaced, or
                      missing. We then used quantum and classical simulations
                      coupled to free-energy calculations to illustrate how, in
                      human DNA Pol-η, the conserved Arg61 favors W–C base
                      pairing through defined interactions with the incoming
                      nucleotide. Taken together, these structural observations
                      and computational results suggest a structural framework in
                      which this specific residue is critical for stabilizing the
                      incoming (d)NTP nucleotide and base pairing during
                      Pol-mediated nucleic acid biosynthesis. These results may
                      benefit enzyme engineering for nucleic acid processing and
                      encourage new drug discovery strategies to modulate Pols
                      function.},
      cin          = {IAS-5 / INM-9},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
      pnm          = {574 - Theory, modelling and simulation (POF3-574)},
      pid          = {G:(DE-HGF)POF3-574},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29424536},
      UT           = {WOS:000427203600026},
      doi          = {10.1021/jacs.7b12446},
      url          = {https://juser.fz-juelich.de/record/844312},
}