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Figure 6.
Figure 6. Active sites of *MtCM (a) and (d), EcCM (b) and
ScCM (c). In the schematic representation (a) of the *MtCM
active site, *MtCM residue labels are boxed and accompanied by
colored labels identifying the corresponding amino acid residues
of EcCM (blue/red; upper labels) and ScCM (green; lower labels).
The homolog of Arg72 in ScCM, Val197 (see Figure 3(a)), forms
part of a wall of the active site pocket, but does not seem to
interact directly with 1 and was therefore omitted. Residues
denoted with an asterisk are functional analogs but not sequence
homologs of Glu106. The transition state analog inhibitor 1 is
highlighted with heavy lines in (a), with yellow carbon atoms in
(b) and (c), and with orange carbon atoms in (d). Hydrogen bonds
are indicated by dotted lines. Note that in *MtCM, the
carboxylate oxygen O2 from inhibitor 1 has three possible
hydrogen bonding partners (with equally favorable geometries):
Arg49, Gln76 and a structural water molecule. This water
molecule, which simultaneously binds to the two carboxylate
groups of inhibitor 1, is tightly coordinated by Arg72 of *MtCM
and Arg51 of EcCM (residue shown only in Figure 6 and Figure 7,
due to crowding in the other pictures; the arginine side-chains
align in an antiparallel fashion with Arg134 and Arg11' of *MtCM
and EcCM, respectively). For *MtCM, the electron density is
shown in stereo representation (s[A]-weighted 2F[o] -F[c] map,
at 1s) (d). (e) and (f) give stereo views of superimpositions of
the three active sites from *MtCM (yellow carbon atoms), EcCM
(red/blue, for the two protomers) and ScCM (green). The view in
(f) is flipped along the horizontal axis of the paper plane,
with respect to the view in (e). Note the differential
positioning (leading to a swap of function) of the residues
corresponding to Val73/Glu106 of *MtCM (Glu52/Val85 in EcCM and
Glu198/Lys243 in ScCM, respectively), which are behind inhibitor
1 in (e) and above the plane in (f).
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