FIGURE 6.

Structural basis for GSI-α-specific Gln feedback inhibition. A, initial F_o − F_c map calculated before the addition of glutamine and metal ions and contoured at 3.2 σ (to 2.95 Å). B, superimposition of active site loops of the glutamine-bound state (green) and the transition state complex (magenta). The Gln-bound active site loops adopt structures similar to apo- and substrate-bound except that the Glu flap (E flap) is well ordered, and the Glu flap residue Glu³⁰⁴ hydrogen-bonds to the Gln as well as the GSI-α-specific residue from the Asp⁵⁰′ loop (D50′ loop), Arg⁶²′. Notably, GSI-β enzymes are not feedback-inhibited by Gln. As shown by the logo, GSI-β enzymes all lack the key Arg⁶²′ residue, explaining why they are not subject to Gln feedback inhibition (in the logo, residues are colored according to type, basic in blue, acidic in red, hydrophobic in black, and glycine/serine in green).