Figure 3.

Depletion soaking induces coordinated movement of the HePTP WPD and E loops. (a) Stereo image of the superposition of the PTP, WPD and E loops of HePTP₀ (blue), HePTP₂₄ (green) and HePTP₂₄₀ (red). In HePTP₀ (blue), the WPD and E loops are well-ordered, and WPD loop residue Asp236 hydrogen bonds with E loop residue Lys182 (illustrated as a dashed line). In crystals depleted of sulfate for 24 hours (i.e. HePTP₂₄; green) and 240 hours (i.e. HePTP₂₄₀; red), the WPD and E loops simultaneously become disordered. Residues in HePTP₂₄ and HePTP₂₄₀ at ordered-to-disordered boundaries are shown in stick representation. The non-superposed PTP, WPD and E loops of HePTP₀, HePTP₂₄ and HePTP₂₄₀ are shown in (b), (c) and (d), respectively. (e) Residue Pro235 adopts the ‘atypically open’ conformation in HePTP₂₄₀. Superposition of the WPD loops from HePTP₀ (blue) and HePTP₂₄₀ (red). In the WPD-closed structure (i.e. HePTP₀; blue), residue Pro240 packs into the hydrophobic pocket formed by Phe231, Trp234, Leu246, and Phe321. In the WPD-open structure (i.e. HePTP₂₄₀; red), residue Pro240 is disordered (illustrated as dashed lines), and residue Pro235 is rotated upward by ~90° (illustrated as a gradated, curved arrow) and instead packs into the Phe231/Trp234/Leu246/Phe321 pocket. The conformation of the conserved WPD loop proline (i.e. Pro235 in HePTP) in HePTP₂₄₀ is identical to that observed in ‘atypically open’ structures of STEP,⁹ Lyp²⁹ and GLEPP1⁶;²⁴. Protein models prepared using PyMOL.³⁶