|
Figure 4.
Fig. 4. Close-up view of F-244 covalently modifying the
BjHMGS1 active site and a posited reaction mechanism based on
the F-244 complex. (A) Secondary structure is shown as ribbons
colored as in Fig. 1. Side chains and F-244 are depicted as
half-colored bonds with red for oxygen, blue for nitrogen, and
gold and gray for carbons on F-244 and HMGS side chains,
respectively. The oxygen atoms of the ring-opened form of F-244
form H-bonds (green dashes) with Glu-83, His-247, and Asn-326
through a water molecule (red sphere) and backbone amides of
Ser-359 and Cys-117. (B) Schematic representation of F-244
tethered to Cys-117 highlighting all intermolecular
interactions. H-bonds are depicted as green dashes. Orange half
circles depict van der Waals contacts with dashed curves
specifying residues sitting behind the plane formed by F-244.
(C) Putative reaction mechanism of HMGS. The proposed role of
Glu-83 in the last hydrolytic step necessary for release of
HMG-CoA is shown in a yellow box. The residues implicated in
formation of the oxyanion hole are depicted in green, and
H-bonds are shown as dashed bonds.
|
