Fig. 4.

Model of allosteric inhibition of TG2 by GTP. Transition from expanded, GTP-free TG2 (upper left) to compact, GTP-bound TG2 (lower right) may occur via an induction mechanism (clockwise) in which GTP binding to the destabilizing Arg-579 (black diamond) triggers a conformational change to the compact form, which is stabilized by Cys-277–Tyr-516 interaction, or a selection mechanism (counterclockwise) in which an unstable conformational intermediate facilitated by Cys-277–Tyr-516 interaction (GTP-free compact, lower left) is stabilized by GTP binding. Removal of the destabilizing Arg-579 by substitution stabilizes the GTP-free compact form in Arg-579 mutants.