Figure 3: Compounds 9 and 15 make a hydrogen bond with Asp-375 within Site A of the active site of LTA₄H.

(a) Green mesh surrounding Compound 9 (orange) shows the Fo-Fc difference map density (2σ level) having omitted the compound from the model. (b) Comparison of X-ray structure of 2H-resveratrol (blue; 3FTU.pdb) and compound 9 (bronze; our study) in Site A of LTA₄H. The protein surface is coloured by amino acid hydrophobicity from most hydrophobic (orange) to hydrophilic (blue) through white regions. (c) Relative positions of 2H-resveratrol (blue) and compound 9 (bronze) showing hydrogen bonding interactions. 2H-resveratrol H-bonds to the carbonyl of Trp-311 and 3 water molecules (pink) and its position is further reinforced by a π-stacking interaction with the indole of Trp-311. Compound 9 adopts a head-to-tail orientation such that its hydroxyl groups form H-bonds to Asp-375, key for hydrolase activity, and a single water molecule (orange). (d) Compound 9 (pink) does not impinge significantly on the peptidase site delineated by OBP-Pro (white; 4MS6.pdb) when the X-ray structures of Compound 9-LTA₄H (our study) and 4MS6.pdb are overlaid. Best scored poses of compound 12 (e; white) and compound 15 (f; orange) docked into site A of LTA₄H with Autodock Vina. The R2 OH of compound 12 is located in a hydrophobic region so replacing this group with a methyl substituent (compound 15) improves interaction with the protein. In addition, a hydrogen-bonding interaction between the phenol of compound 15 and Asp-375 is also observed.