1hd7: Difference between revisions

==Overview==

The major human abasic endonuclease, Ape1, is an essential DNA repair, enzyme that initiates the removal of apurinic/apyrimidinic sites from DNA, excises 3' replication-blocking moieties, and modulates the DNA binding, activity of several transcriptional regulators. We have determined the, X-ray structure of the full-length human Ape1 enzyme in two new crystal, forms, one at neutral and one at acidic pH. The new structures are, generally similar to the previously determined structure of a truncated, Ape1 protein, but differ in the conformation of several loop regions and, in spans of residues with weak electron density. While only one, active-site metal ion is present in the structure determined at low pH, the structure determined from a crystal grown at the pH optimum of Ape1, nuclease activity, pH 7.5, has two metal ions bound 5 A apart in the, active site. Enzyme kinetic data indicate that at least two metal-binding, sites are functionally important, since Ca(2+) exhibits complex, stimulatory and inhibitory effects on the Mg(2+)-dependent catalysis of, Ape1, even though Ca(2+) itself does not serve as a cofactor. In, conjunction, the structural and kinetic data suggest that Ape1 catalyzes, hydrolysis of the DNA backbone through a two metal ion-mediated mechanism.

==About this Structure==

[[Category: ref-1]]