Structure of alkaline phosphatases

Abstract

The crystal structure of alkaline phosphatase (AP) from Escherichia coli, which is a prototype for mammalian APs, has been refined to a crystallographic R-factor of 0.184 at 2.0 A resolution. During the course of the refinement residues 380 to 410 were retraced and 190 to 200 were shifted by one residue, and substantial changes in the active site of the enzyme were made. Based on the refined structure and the sequences of mammalian enzymes (25-30% strict homology) we have modelled the core of the three dimensional structures of the mammalian alkaline phosphatases. Considerable circumstantial evidence suggests that this is valid despite the fact that the mammalian enzymes are larger, contain carbohydrate and are membrane associated through a phosphatidylinositol moiety. The active site of the molecule is highly conserved but specific changes in the secondary ligands to bound phosphate and the Mg metal are observed.