Crystal structure
of AfNMT complexes with inhibitors. (A) Overall fold
of AfNMT (residues 86–492) in complex with
MCoA (stick representation, Cα cyan) and RO-09-4879
(stick representation, Cα green). (B) Representative
crystal structures of NMTs. AfNMT shown in gray cartoon
superimposed upon ScNMT (PDB 1IIC, green), LmNMT (PDB 3H5Z, magenta), HsNMT1 (PDB 3IU1, cyan), and PvNMT (PDB 4B10, orange). (C) Conservation
of NMT active site residues. AfNMT backbone shown
in gray cartoon with active site side chains shown in stick representation
(C atoms gray). Strictly conserved residues between species are shown
for AfNMT only. Where residues are not conserved,
they are shown for all species in stick representation, ScNMT (green), LmNMT (magenta), HsNMT1 (cyan), and PvNMT (orange). (D) Close-up view
of the AfNMT active site, showing the MCoA (Cα cyan) and RO-09-4879 (Cα green). A
molecular surface is shown, colored by sequence conservation with HsNMT1 (gray, identical side chains; purple, nonidentical
side chains). (E) Stereoscopic view of the active site of the AfNMT in complex with DDD85646 and DDD86481. Active site
side chains are shown as sticks with gray Cα, whereas
the compound is shown as sticks with gold Cα. The
unbiased |Fo| – |Fc| map (2.5 σ) is shown as a green mesh.