Chemistry Reference
In-Depth Information
Figure 15.1
Phosphoryl transfer reactions in nucleic acid synthesis, cleavage and recombina-
tion: (A) DNA and RNA synthesis. An incoming (d)NTP is incorporated into the primer strand.
The 3
-OH of the primer strand is the nucleophile and attacks the
a
-phosphate of (d)NTP
(highlighted in red). Pyrophosphate (PPi) is the leaving group. (Reproduced from Yang, W.
et al.
, Making and breaking nucleic acids: two-Mg
2+
-ion catalysis and substrate specifi city,
Mol. Cell
, 2006,
22
, 5-13); (B) Cleavage. Scissile phosphate (highlighted in red) is transferred
to water (hydrolysis), a nucleotide (as in splicing), a Tyr or Ser protein side chain (as in DNA
recombination), or another DNA or RNA strand (as in RNA splicing or DNA recombination)
depending on the nucleophile. The products are 3
′
′
-OH and 5
′
-PO
4
. (
C
) Same as (B) except
the products are 5
′
-OH and 3
′
-PO
4
confi guration at the phosphorus.
9 - 11
A nucleophile can attack the scissile phosphate
from either side of the phosphate, and thus either the 3
- OH can be the leaving
group
4,5,12
(Figure 15.1B,C). To date, except for catalysis that results in a 3
′
- or 5
′
′
- phosphate
- OH,
4,6
one or two metal ions are required for the phosphoryl transfer
reaction.
and a 5
′
15.1.1 Basic Properties of Mg
2+
and Divalent Cations
Mg
2+
and Ca
2+
are the most abundant divalent cations in living organisms,
13,14
and
Mg
2+
is the most abundant divalent cation inside cells.
15,16
Others, like Fe
2+
, and Zn
2+
and Cu
2+
are widespread, and Mn
2+
and Ni
2+
are essential, but found at low concen-
trations.
14
The foremost quality of these divalent cations is the high density of posi-
tive charge, which makes them effi cient for charge neutralization of phospholipids
and nucleic acids. The second common property is hydration and the specifi c ligand
requirement. By the atomic or covalent radius Ca
2+
is the largest (1.9 Å ), Mg
2+
the
second (1.6 Å) and the rest are similarly smaller (1.3 Å). However, when hydrated,
Mg
2+
is larger than Ca
2+
because Mg
2+
is associated with multiple shells of ligand
water molecules.
16
In biological systems these metal ions never exist without water
