Structure of APE1
APE1 contains several amino acid residues that enable it to react selectively with AP sites. Three APE1 residues (Arg73, Ala74, and Lys78) contact three consecutive DNA phosphates on the strand opposite the one containing the AP site while Tyr128 and Gly127 span and widen the minor groove, anchoring the DNA for the extreme kinking caused by the interaction between positive residues found in four loops and one α-helix and the negative phosphate groups found in the phosphodiester backbone of DNA.
This extreme kinking forces the baseless portion of DNA into APE1’s active site. This active site is bordered by Phe266, Trp280, and Leu282, which pack tightly with the hydrophobic side of the AP site, discriminating against sites that do have bases. The AP site is then further stabilized through hydrogen bonding of the phosphate group 5´ to the AP site with Asn174, Asn212, His309, and the Mg2+ ion while its orphan base partner is stabilized through hydrogen bonding with Met270. The phosphate group 3' to the AP site is stabilized through hydrogen bonding to Arg177. Meanwhile, an Asp210 in the active site, which is made more reactive due to the increase in its pKa (or the negative log of acid dissociation constant) caused through its stabilization through its hydrogen bonding between Asn68 and Asn212, activates the nucleophile that attacks and cleaves the phosphodiester backbone and probably results in the observed maximal APE1 activity at a pH of 7.5.
Read more about this topic: AP Endonucleases
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