The bound geometry of adduct 6 gave acceptable validation metrics, which were superior to the original model of BU72, 1a (Table ; data in Additional file 7). The only severe outlier was the bond angle at the bridging oxygen (131° vs the ideal, 109°: Z = 7.2). There are several indications that this is real strain rather than a fitting artefact, however. The angle is clearly resolved at high density, and is consistent with tension from the tethered N-terminus. The phenyl group is bent 11° out of plane, consistent with being pulled against the adjacent residue Ile144 3x29 by the same tension (Figure ). This bend is also clearly resolved, and is comparable to those seen in severely strained aromatic residues at subatomic resolution . It also yields a more complementary fit to Ile144 3x29 than the original model, as well as eliminating another small pocket of unexplained density (Figure ). Despite the very strong interactions apparent between BU72 and His54, removal of the side chain of His54 by receptor mutagenesis had no detectable effect on the affinity or potency of BU72 . This seeming paradox, however, is consistent with the mechanism proposed here. Since the full-length receptor was used for the assays, the Gly-Xaa-His motif was not at the N-terminus, and therefore nickel complexation and adduct formation could not occur. Thus, binding would be unaffected by the presence or absence of His54.