期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2022.824794
关键词
two-metal-ion catalysis; third inhibitory divalent metal ion; bell shaped pol activity plots; Hill coefficient; Bronsted equation
Almost all DNA polymerases exhibit bell-shaped activity curves as a function of both pH and Mg2+ concentration. The activity of the polymerase is reduced when the pH deviates from the optimal value or when the concentration of divalent metal ions is too low or too high. The role of the third metal ion in the polymerase activity is currently controversial.
Almost all DNA polymerases (pols) exhibit bell-shaped activity curves as a function of both pH and Mg2+ concentration. The pol activity is reduced when the pH deviates from the optimal value. When the pH is too low the concentration of a deprotonated general base (namely, the attacking 3 '-hydroxyl of the 3 ' terminal residue of the primer strand) is reduced exponentially. When the pH is too high the concentration of a protonated general acid (i.e., the leaving pyrophosphate group) is reduced. Similarly, the pol activity also decreases when the concentration of the divalent metal ions deviates from its optimal value: when it is too low, the binding of the two catalytic divalent metal ions required for the full activity is incomplete, and when it is too high a third divalent metal ion binds to pyrophosphate, keeping it in the replication complex longer and serving as a substrate for pyrophosphorylysis within the complex. Currently, there is a controversy about the role of the third metal ion which we will address in this review.
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