Fig 1.
A) SAAT homology model. Helix structures are colored in red, while beta-sheet structures in cyan. The motif HXXXD is represented in licorice representation on green, while the highly conserved DFGWG motif is represented in ball and stick representation on blue B) Electrostatic surface potential at SAAT front face. C) Electrostatic surface potential at SAAT back face. The potential energy surface was measured by Pymol v1.6 software (The PyMOL Molecular Graphics System, Version 1.6 Schrödinger, LLC.) using APBS plugin [41].
Fig 2.
Main established interactions by Acetyl-CoA at the front face pocket in SAAT
. SAAT is shown in white ribbon representation and acetyl-CoA is represented in balls and sticks with carbon atoms colored in green. Residues His157, Asp166, Asn182 and some positive charged residues (Arg177 and Arg180, which are establishing hydrogen bond interactions with the phosphate groups of the CoA) are shown in licorice representation with carbon atoms colored in grey. Hydrogen bonds between Acetyl-CoA and Arg and Asp residues are depicted as black dashed lines.
Fig 3.
Superposition of molecular docking conformations obtained for four alcohol substrates and acetyl-CoA at the back face pocket of SAAT.
Octanol, butanol, hexanol and benzyl alcohol are represented as sticks colored in blue, orange, red and grey, respectively. Acetyl-CoA and His157 are represented in ball and sticks with carbon atoms colored in green and grey, respectively. The hydrogen bonds between Nε of His157 and hydroxyl group of alcohol substrates are represented as black dashed lines.
Table 1.
Comparison of substrate specificity of SAAT and molecular docking energies for the different acetyl-CoA-alcohol-SAAT modeled complexes that could promote the synthesis of the corresponding ester.
Fig 4.
Main distances established between ligands and catalytic residues at the SAAT active site during 30 ns of MD simulations.
(A) Distances between the oxygen atom of the alcohols and the carbonylic carbon of the acetyl-CoA (dHO•••O = C-AcCoA); (B) Distances between the oxygen atom of the alcohols and the Nε of the His157 (dHO•••Nε-His157). Distances for octanol, hexanol, butanol and benzyl alcohol are represented in black, red, blue and green lines, respectively.
Table 2.
Free binding energies and its components calculated from MM-GBSA approach.