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. Author manuscript; available in PMC: 2017 Nov 29.
Published in final edited form as: Biochemistry. 2016 Nov 11;55(47):6484–6494. doi: 10.1021/acs.biochem.6b00859

Figure 6.

Figure 6

Mechanism of IGPS allosteric signal disruption by inhibitor binding. Changes in ionic interactions among the fα2, fα3, and hα1 helices (bottom row) in the apo IGPS complex (blue, center column) induced by PRFAR binding (red, right column) and subsequently altered by inhibitor binding (black, left column). Disruption of the allosteric signal launched by PRFAR manifested as hampered oxyanion strand flip, which is initiated on the submicrosecond time scale in the binary complex while absent in the 3–IGPS ternary complex (middle row). The flip of the 49-PGVG strand is crucial for glutaminase activity because it allows stabilization of a four-center intermediate (FCI) in the oxyanion hole (top row).