TY  - JOUR
AU  - Genna, Vito
AU  - Vidossich, Pietro
AU  - Ippoliti, Emiliano
AU  - Carloni, Paolo
AU  - Vivo, Marco De
TI  - A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases
JO  - Journal of the American Chemical Society
VL  - 138
IS  - 44
SN  - 1520-5126
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2016-05997
SP  - 14592 - 14598
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000387625300018
C6  - pmid:27530537
DO  - DOI:10.1021/jacs.6b05475
UR  - https://juser.fz-juelich.de/record/820729
ER  -