Chemistry Reference
In-Depth Information
Figure 6.26 Active sites of (A) DNA polymerase and (B) 3
0
,5
0
-exonuclease.
DNA chain. Based on crystal data, Steitz and Beese [135] proposed an interesting me-
chanism for the dinuclear metalloenzyme catalyzed hydrolysis of DNA [Figure
6.26(B)]. The proposed mechanism for the breakdown of DNA is remarkably similar
to that proposed for DNA synthesis, involving activations by metal hydroxide, leaving
group and two Lewis acids [136]. In DNA synthesis, the leaving group is already a good
one and the leaving oxygen does not need to be directly coordinated to the metal.
In model systems (
6
), up to 10 orders of magnitude rate acceleration has been ob-
tained by combining Lewis acid and metal-hydroxide activations [43, 53]. Leaving-
group activation is expected to be additive to Lewis acid and metal-hydroxide activa-
tions since
6
provides comparable rate acceleration for hydrolyzing phosphate diesters
with good or poor leaving groups. If the metal lowers the basicity of the leaving group
by 10 log units, the rate of hydrolysis should increase about ten million-fold since the
