Figure 5. MES Ligand Binding Pockets in Trigonal 3mbt Structures.

(A) Superimposition of three mbt repeats with bound MES molecules in the seleno-met structure. A MES molecule (labeled 1, 2, and 3) is bound to each β subunit core (colored as in Figure 2A).

(B) The mutation sites are located in and around the MES binding pocket (second mbt repeat) in the 3mbt structure (seleno-met). The morphilino ring of the bound MES molecule (red) is encapsulated by polar and aromatic residues (silver). The electron density for bound MES is shown in a chicken wire representation. Residues that are point mutated (magenta) and deleted (blue) are highlighted with the letters M and D, respectively. Residue M357 in the second repeat is included, since it occupies a position analogous to R461 in the third repeat (see [C] and [D]). Hydrogen bond networks are indicated by dotted lines (magenta). Oxygen and nitrogen atoms are colored red and blue, respectively.

(C) The surface representation of the open form of the MES (yellow) binding pocket from the third mbt repeat in the seleno-met structure. Residues lining this pocket are indicated in black. Arginine R461 is indicated in dotted surface (pink) representation with its side chain in a stick mode (white). Conserved residues among mbt repeats that are mutated in the SCM protein (Bornemann et al., 1998) are explicitly indicated in blue (deletion mutations, labeled D) and red (point mutations, labeled M).

(D) The surface representation of the closed form of the MES binding pocket from the third mbt repeat in the GTP-containing native 1 structure. The R461 arginine finger flips its long and bulky side chain into the pocket, closing this site to MES ligands. This alignment is stabilized by a single hydrogen bond with residue D459 (point mutated in mbt of SCM protein; Bornemann et al., 1998).