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Catalytic mechanism of DNA polymerases-Two metal ions or three?

Catalytic mechanism of DNA polymerases-Two metal ions or three?

Protein Sci. 2019 Feb;28(2):288-291
doi: 10.1002/pro.3542

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摘要

The catalysis by DNA polymerases has been thought for decades to go through a two‐metal‐ion mechanism [Fig. 1(a)], involving Metal A (MeA, catalytic metal) and Metal B (MeB, nucleotide binding metal). Since 2012, a third metal, Metal C (MeC), has been observed for Pol η,1, 2 Pol β,3-7 and Pol μ8 by time‐lapse X‐ray crystallography. For Pol β and Pol μ, reported by Wilson, Perera and coworkers, the role of MeC has been suggested to be in product stabilization.3, 4, 8-10 On the other hand, MeC has been suggested to play a key catalytic role in a new “three‐metal‐ion mechanism” [Fig. 1(b)] based on detailed crystallographic studies as well as kinetics and mutagenesis.2, 11 The results of Pol β on 8‐oxoG lesion by Suo's group also supported the catalytic role of the third metal.5, 6, 12 Since the two‐metal‐ion mechanism has been shown to be conserved among DNA polymerases as well as other related enzyme families, it is important to determine which of the two “competing mechanisms” is correct.