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Unified two‐metal mechanism of RNA synthesis and degradation by RNA polymerase
Author(s) -
Sosunov Vasily,
Sosunova Ekaterina,
Mustaev Arkady,
Bass Irina,
Nikiforov Vadim,
Goldfarb Alex
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg193
Subject(s) - polymerase , rna , nucleoside triphosphate , chemistry , base pair , nucleoside , active site , rna polymerase , stereochemistry , dna , biophysics , biochemistry , combinatorial chemistry , catalysis , biology , nucleotide , gene
In DNA‐dependent RNA polymerases, reactions of RNA synthesis and degradation are performed by the same active center (in contrast to DNA polymerases in which they are separate). We propose a unified catalytic mechanism for multisubunit RNA polymerases based on the analysis of its 3′–5′ exonuclease reaction in the context of crystal structure. The active center involves a symmetrical pair of Mg 2+ ions that switch roles in synthesis and degradation. One ion is retained permanently and the other is recruited ad hoc for each act of catalysis. The weakly bound Mg 2+ is stabilized in the active center in different modes depending on the type of reaction: during synthesis by the β,γ‐phosphates of the incoming substrate; and during hydrolysis by the phosphates of a non‐base‐paired nucleoside triphosphate. The latter mode defines a transient, non‐specific nucleoside triphosphate‐binding site adjacent to the active center, which may serve as a gateway for polymerization of substrates.