Fig. 7
Analysis of sEH binding modes for 15d-PGJ2. a Protein sequence alignment. Alignment of sEH amino acid sequences of different species, highlighting C423 and C522 in the top and bottom panel respectively. The red boxes highlight the reactive cysteine residues. The secondary structure reported above the alignments refers to the human apo sEH structure. The histograms represent the conservation score calculated by Jalview71 (*full conservation, +: full properties conservation). b Proposed dock-and-lock binding mechanism. In a first fast step, 15d-PGJ2 docks non-covalently in the hsEH CTD binding site (docked state). This is followed by the formation of a covalent complex (locked state), and this step is characterised by a slower kinetics. c 15d-PGJ2 binding position compared to previously characterised orthosteric inhibitors 4XH, CDU, S0J. The surfaces represent the Phe267 Pocket (magenta), the Vertex (blue) and the Trp334 Niche (cyan), while residues C423 and C522 are reported in orange. The superposition herein reported was performed using PDBs 1EK247, 3WKC72 and 5AI649
