Chemistry Reference
In-Depth Information
ATP
ADP
Mg
2+
Mg
2+
E
1
~P
3Na
+
E
1
3Na
+
E
1
ATP
3Na
+
1. ATP binding
2. Formation of
« high-energy » aspartyl
Phosphate intermediate
3Na
+
(in)
2K
+
(in)
Inside
6. K
+
transport and
Na
+
binding
3. Na
+
transport
Outside
3Na
+
(out)
5. Phosphate
hydrolysis
4. K
+
binding
E
2
_
P
E
2
_
P
2K
+
E
2
2K
+
P
i
H
2
O
2K
+
(out)
A model for the active transport of Na
þ
and K
þ
by the Na
þ
-K
þ
-ATPase.
FIGURE 9.9
(Adapted from
Voet & Voet, 2004
.
)
dephosphorylation of the E
2
-P form of the enzyme, is the basis for a number of steroid drugs which are commonly
prescribed for the treatment of congestive heart failure.
The structures of a number of P-type ATPases, including the Na
þ
-K
þ
-ATPase, have been determined. They
have a common overall domain organisation of the main catalytic (
a
-) subunit (
Figure 9.10
): six to twelve
FIGURE 9.10
-subunit with 10 TM
helices. (b) Sequence conservation among human P-type ATPases. Highly conserved residues (magenta spheres) cluster in the P-domain.
(From
Bublitz et al., 2010
.
Reproduced with permission from Elsevier.)
PDB structures and conservation of P-type ATPases. (a) Topology diagram of a typical P-type ATPase
a
a
-helices which make up the ion transport domain and three cytoplasmic domains, the N-domain (nucleotide
binding), P-domain (phosphorylation), and A-domain (actuator), which confer the ATP hydrolysing activity. The
N-domain positions the
-phosphoryl of ATP for nucleophilic attack, a conserved Asp in the P-domain accepts the
phosphoryl group and forms a high-energy aspartyl-phosphate, while a Glu residue in the A domain positions
a water molecule for subsequent hydrolysis, which leads to release of the phosphoryl group. The overall structures
g
