Figure 1.

New crystal structure of human APE1 with the native Mg²⁺ cofactor and previous structures with surrogate metals. (a) Close-up view of the active site of the new structure, showing Mg²⁺ and several ordered water molecules (molecule A of the three molecules in the asymmetric unit for PDB entry 4lnd). Also shown are the important catalytic residues; all but Asp70 are strictly conserved in the DNase I superfamily (Tyr171 is replaced by His in some members). The octahedral coordination of Mg²⁺ is indicated by dotted lines with distances provided (also given in Table 3 ▶). Hydrogen bonds are indicated by dashed lines. (b) The same view of the active site showing a 2F _o − F _c OMIT map contoured at 1.5σ for protein and waters and an F _o − F _c OMIT map contoured at 8.0σ for the Mg²⁺ ion (black mesh). Note that one or more of the three non-Mg²⁺-coordinating water molecules are not observed in the other two protein molecules (B and C) in the asymmetric unit. (c) Previously reported structure of Sm³⁺-bound APE1 (green; PDB entry 1bix; Gorman et al., 1997 ▶) aligned with the new Mg²⁺-bound structure (white). The coordination of the Sm³⁺ ion (cyan) is shown (dotted lines) with distances. The coordination of Mg²⁺ (green) in the new structure is also indicated (without distances). Water molecules shown as red spheres and hydrogen bonds (dashed lines) are for the Sm³⁺-bound structure. The water molecules that coordinate Mg²⁺ are shown as red stars. (d) The previously reported structure of APE1 with one Pb²⁺ ion (green; PDB entry 1hd7; Beernink et al., 2001 ▶) aligned with the new Mg²⁺-bound structure (white). The coordination of the Pb²⁺ ion (gray) is shown (dotted lines) with distances and the coordination of Mg²⁺ (green) is also indicated. Water molecules (red spheres) and hydrogen bonds (dashed lines) are for the Pb²⁺-bound structure (waters that coordinate Mg²⁺ are shown as red stars). (e) The previously reported structure of APE1 with two Pb²⁺ ions (green; PDB entry 1e9n; Beernink et al., 2001 ▶) aligned with the new Mg²⁺-bound structure (white). The coordination of the Pb²⁺ ions (gray) is shown (dotted lines) with distances and the coordination of Mg²⁺ (green) is similarly indicated. Water molecules (red spheres) and hydrogen bonds (dashed lines) are for the Pb²⁺-bound structure (waters that coordinate Mg²⁺ are shown as red stars).