Figure 6.

The active site and inhibitors bound from high-resolution crystal structures of hGIIA complexes. Amino acids are depicted if they are within 5 Å of any atom of either inhibitor or the catalytic Asp 99. In addition, contiguous elements of the representation of the main chain of 3 helices (transparent pink cartoon) are provided to aid in an orientation comparison with Figure 2. The carbons of the inhibitors and calcium are coloured mauve. The active site cavity opening is most obviously bounded by Leu2, His6, Ala18, Phe24 and Val31. The main chain of Cys29, Gly30 and Val31 have been removed from the foreground and, as a consequence, the coordination of the calcium by O(Gly 30) is not indicated in both structures or an N(Gly 30) interaction with a phosphonyl oxygen of the transition state analogue. (a) The transition state analogue (TSA) L-1-O-octyl-2-heptyl-phosphonyl-sn-glycero-3-phosphoethanolamine (PDB ID 1POE at 2.1 Å resolution [156]). The two hydrophobic chains of the TSA are relatively parallel, and this structure is the best understanding of the native substrate orientation at the active site channel. The end 3 carbons on the sn-1 chain were not determined, but nevertheless the sn-1 chain is in proximity to the Leu2, Gly30, Val31 and Tyr52, and the sn-2 with Phe5, Ala18, and Gly23; (b) The LY311727 (PDB ID 3U8D at 1.8 Å resolution [13]). The two views have been chosen to be similar. For LY311727 the hydrophobic interactions are provided by Leu2, Phe5, His6, Leu20 and Gly30. Figure was created with PyMOL [14].