Figure 5.

Three-dimensional structures of human β-tubulin, PKM2 and their interactions with arsenic. A) Homology model of human β2-tubulin based on the X-ray structure of bovine β-tubulin (PDB code: 1JFF), and its binding by arsenic at Cys¹². For comparison, all the Cys residues of human β2-tubulin are represented in ball-and-stick depiction: Cys¹², Cys²⁰³, Cys²¹³ and Cys³⁰⁵ are located near the GTP binding site, while Cys¹²⁹, Cys¹³¹, Cys²⁴¹ and Cys³⁵⁶ are distantly located from the GTP binding site and near the interface with the α subunit. The α-helical motif containing Cys²¹³ and the adjacent loop labile to structural modification are colored in blue. B) Plausible conformation of human β-tubulin with Cys¹² and Cys²¹³ bound by arsenic. The α-helical motif containing Cys²¹³ (Glu²⁰⁷-Tyr²²⁴) has been modified accordingly. This motif and the adjacent loop labile to structural modification are colored in red. Hydrogen atoms are omitted to clarify the view. C) GTP-binding site of human β-tubulin indicated by dot depiction (in magenta). The closest Cys residue from the active site is Cys¹² with a distance of 2.60Å between the GDP sugar ring oxygen and the side chain sulfur of Cys¹². D) Active site of human PKM2 (PDB code: 1T5A), indicated by dot depiction (in magenta) for oxalate and phosphate. The closest Cys residue from the active site is Cys³²⁶ with a distance of 13.80Å between the active site Mg²⁺ and the side chain sulfur of Cys³²⁶. Color coding: green, C; red, O; blue, N; yellow, S; and magenta, phosphate and arsenic.