The PTP1B catalytic cycle and its allosteric control (free/open, outer circle; inhibitor bound/closed, inner circle).
(A→B) Binding of the active site inhibitor TCS401 pushes the W179 aromatic side chain towards P185 (P185 makes a CH/π switch from F269 to W179).
(C→D) This allows for the closing of the WPD loop.
(E→F) The resulting ‘F191 push’ causes helix α3 to rotate.
(G→H) This allows S190 to hydrogen bond with S187, extending and stabilizing helix α3.
(I→J) This allows N193 to interact with Y152 and E295.