FIGURE 6.

Rotamer transitions revealed by the high-resolution crystal structures of the Na⁺,K⁺-ATPase. Site I coordination in the E₁·AlF₄⁻·ADP·3Na⁺ structure (A, PDB code 3WGU, Ref. 18), and the E₂·MgF₄²⁻·2K⁺ structure (B, PDB code 2ZXE, Ref. 30). The figure shows site I and the position of important M5 residues as well as the side chains of Thr⁷⁸¹, Phe⁷⁸³, and Phe⁷⁸⁶ (kidney sequence), located near the extracellular surface. A, the hydroxyl group of Thr⁷⁷² is coupled to a Na⁺ in site I. The hydroxyl group of Thr⁷⁷⁴ is contacting a Na⁺ in site III (shown in gray). The side chains of Phe⁷⁸³ and Phe⁷⁸⁶ bend toward the extracellular side. B, the methyl group of Thr⁷⁷² is connected to a K⁺ in site I through water molecules. The side chain of Thr⁷⁸¹ is disconnected from “empty site III.” The side chains of Phe⁷⁹⁰ and Phe⁷⁹³ (shark sequence) are moved toward the cytoplasm (compare with their position to that in the E₁ structure). Note that the side chain of Thr⁷⁸¹ (Thr⁷⁸⁸ in the shark sequence), located away from the cytoplasmic side, does not adopt rotamer transition, i.e. the side chain has the identical position in both structures. Note the close proximity of Asp⁸⁰⁸ (Asp⁸¹⁵ in the shark sequence) to the Na⁺ in site I compared with its position in the E₂ structure, this insertion (likely facilitated by the movement of M6) seems to regulate the traffic of water molecules into the binding cavity around site I. Note also that the side chain of Asn⁷⁷⁶ also seems to adopt a rotation, directing the side chain hydroxyl toward K⁺ in site I in the E₂ structure (Asn⁷⁸³ in shark sequence). The figure was made using PyMOL.