FIGURE 8.

Proposed reaction mechanism of TnDhp. A, the open form of the tunnel enables the substrate to diffuse into the active site. Dashed circle, Mβ binding site. Oblongs, the dynamic loops Ala⁶⁹–Arg⁷⁴ and Met¹⁵⁸–Met¹⁶⁵, in which Phe⁷⁰ and Tyr¹⁶⁰ are labeled. Dashed lines, interactions. B, two dynamic loops shift to the closed form (dashed oblong to the solid line) and lock the substrate in the specific position. The carbamylated lysine 155 (Kcx¹⁵⁵) may assist the substrate binding and catalysis. C, the water undergoes nucleophilic attack and generates putative products. The interactions between product and Tyr¹⁶⁰ observed in the structures of the complex may indicate the involvement of Tyr¹⁶⁰ in the stabilization of the intermediate state (dashed line). D, the C terminus from another monomer helps to open the tunnel, and the substrate diffuses out of the active site.