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Figure 3.
Figure 3. Conformational states and comparison of AC enzymes.
(a) Structure-based sequence alignment of bicarbonate responsive
sAC enzymes and the G protein -regulated tmAC domains VC[1] and
IIC[2] (PDB entry 1AZS). Secondary structure elements of sAC and
IIC[2] are indicated on top and bottom, respectively.
Ion-binding residues (  )
and residues binding the substrate (^) or the transition state (
 )
are labeled (filled and empty symbols label C[1] and C[2]
residues, respectively). Thr1139^* and the insertion
characteristic for sAC enzymes are indicated (  ).
Conserved amino acids are shaded yellow, and residues with
conserved physicochemical properties are shaded red. (b) Overlay
of the sAC -  ,
 -Me-ATP
structure (open state, darkest gray, with 1
helix and 7
- 8
loop in blue), the sAC -Rp-ATP S
complex (partially closed, middle gray and red), and the
bicarbonate-soaked Rp-ATP S
structure (closed, lightest gray and yellow). Structures were
superimposed on sAC - ,
-Me-ATP
by optimizing positional agreement for residues 1014 -1018, 1056
-1065, 1117 -1126 and 1143 -1167 in both subunits. (c) sAC
active site in complex with Rp-ATP S
and two magnesium ions, with the two monomers colored red and
blue, respectively. The dashed lines indicate the octahedral
coordination of the ions through the ATP analog, protein
residues and one and two water molecules (gold spheres),
respectively. The 2F[o] - F[c] omit electron density for the
ligands was contoured at 1.1  .
In its tmAC complex, P of
Rp-ATP S
was modeled differently but with limited electron density for
the ribose and its link to the P 16,
and we speculate that this density might also be interpretable
with the inhibitor conformation observed here for its sAC
complex.
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