Ternary complex of Eg5 motor domain with monastrol and ADP-Magnesium. Ternary complex of Eg5 motor domain with monastrol and ADP-Magnesium. (A) Ribbon diagram of the Eg5 motor domain (pale blue) with the nucleotide binding site facing down, containing ADP-Magnesium (adapted from PDB: 1Q0B). Monastrol is bound 12 Å from the nucleotide binding pocket, in a pocket formed by residues in α2 (green, labeled 'a2'), α3 (yellow, labeled 'a3') and loop 5 (red), a structural feature interrupting α2. (B) Stereoscopic view of monastrol binding site to illustrate the hydrophobic dihydropyrimidine binding surface between α2 and α3 formed primarily by the side chains of amino acid residues E116, I136, P137, Y211, L214, and A218. The van der Waals contact surface of Eg5 is labeled with its corresponding amino acid residue and is colored gray for carbon, red for oxygen, and blue for nitrogen. (C) The hydroxyphenyl ring is oriented perpendicular to the plane of the dihydropyrimidine ring in a hydrophobic pocket bounded by the side chains of amino acid residues R119, W127, A133, and Y211. Two potential hydrogen bonding interactions between monastrol and the backbone carbonyls oxygens of amino acid residues E116 and E118 are highlighted in red. Distances from monastrol N to E116 and O to E118 are 2.82 Å and 2.73 Å, respectively.
Maliga and Mitchison BMC Chemical Biology 2006 6:2 doi:10.1186/1472-6769-6-2