TY  - JOUR
AU  - Genna, Vito
AU  - Colombo, Matteo
AU  - De Vivo, Marco
AU  - Marcia, Marco
TI  - Second-Shell Basic Residues Expand the Two-Metal-Ion Architecture of DNA and RNA Processing Enzymes
JO  - Structure
VL  - 26
SN  - 0969-2126
CY  - London [u.a.]
PB  - Elsevier Science
M1  - FZJ-2017-08381
SP  - 40-50
PY  - 2018
AB  - Synthesis and scission of phosphodiester bonds in DNA and RNA regulate vital processes within the cell. Enzymes that catalyze these reactions operate mostly via the recognized two-metal-ion mechanism. Our analysis reveals that basic amino acids and monovalent cations occupy structurally conserved positions nearby the active site of many two-metal-ion enzymes for which high-resolution (<3 Å) structures are known, including DNA and RNA polymerases, nucleases such as Cas9, and splicing ribozymes. Integrating multiple-sequence and structural alignments with molecular dynamics simulations, electrostatic potential maps, and mutational data, we found that these elements always interact with the substrates, suggesting that they may play an active role for catalysis, in addition to their electrostatic contribution. We discuss possible mechanistic implications of this expanded two-metal-ion architecture, including inferences on medium-resolution cryoelectron microscopy structures. Ultimately, our analysis may inspire future experiments and strategies for enzyme engineering or drug design to modulate nucleic acid processing.
LB  - PUB:(DE-HGF)16
C6  - pmid:29225080
UR  - <Go to ISI:>//WOS:000419101700007
DO  - DOI:10.1016/j.str.2017.11.008
UR  - https://juser.fz-juelich.de/record/841290
ER  -