Fig. 2: Crystal structure of human TNF with UCB-6876.
From: Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer
a Top and side views of TNF (green ribbons) with UCB-6876 bound (orange sticks). b Detail showing the electron density of UCB-6876 and MPD bound within the TNF homotrimer. Monomers B (light green) and C (green) are shown surface rendered. Contour level of the electron density is set at 1 sigma. MPD occupies a space next to UCB-6876. Subsequent molecules described in this paper were modified to have chemical groups occupying the space where MPD was bound. c Detail of the compound-binding pocket within the TNF homotrimer, with key residues involved in binding highlighted (sticks and labels). d Side view of apo-TNF (left image) and UCB-6876 bound TNF (right image) revealing the distorted AC receptor-binding site (selected residues involved in TNFR1 binding are highlighted red).
