Refined structures of placental alkaline phosphatase show a consistent pattern of interactions at the peripheral site

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Aug 1;66(Pt 8):866-70. doi: 10.1107/S1744309110019767. Epub 2010 Jul 27.

Abstract

In order to gain deeper insights into the functional sites of human placental alkaline phosphatase, the structures of the enzyme with the putative regulators L-Phe, pNPP and 5'-AMP [Llinas et al. (2005), J. Mol. Biol. 350, 441-451] were re-refined. Significant variations in ligand positioning and identity were found compared with the previous report. The multiple corrections to the model improved the phases and the electron-density maps, allowing the modeling of omitted side chains and multiple disordered residues. These improvements led to a change in the position of L-Phe at the peripheral binding site, which appeared to be reversed. The structure with pNPP contained only p-nitrophenol in three distinct sites, while the structure with 5'-AMP contained the p-nitrophenyl group in two of the sites instead of 5'-AMP. Comparison of the re-refined models shows a consistent pattern of interactions at the peripheral site.

MeSH terms

  • Alkaline Phosphatase / chemistry*
  • Crystallography, X-Ray
  • Female
  • Humans
  • Models, Molecular
  • Placenta / enzymology*
  • Pregnancy
  • Protein Interaction Domains and Motifs*
  • Protein Structure, Quaternary

Substances

  • Alkaline Phosphatase

Associated data

  • PDB/3MK0
  • PDB/3MK1
  • PDB/3MK2