Effects of Cu2+ on alkaline phosphatase from Macrobrachium rosenbergii

Int J Biol Macromol. 2018 Oct 1:117:116-123. doi: 10.1016/j.ijbiomac.2018.05.165. Epub 2018 May 23.

Abstract

To gain insight into the effect of Cu2+ on the activity and structure of alkaline phosphatase (ALP) from Macrobrachium rosenbergii, the enzyme was purified using ammonium sulfate fractionation, Sephacryl S-200, and DEAE anion exchange chromatography. We studied Cu2+-mediated inhibition and aggregation of ALP, and found that Cu2+ significantly inactivated ALP activity with an IC50 of 1.47 ± 0.02 mM. We further revealed that Cu2+ reversibly inhibited ALP in a mixed-type manner with Ki = 0.41 ± 0.02 mM. Time-interval kinetics showed that the inhibition followed first-order reaction kinetics. This process was associated with conformational changes and significant transient free-energy change. Spectrofluorometry results showed that Cu2+ induced ALP tertiary structural changes, including the exposure of hydrophobic surfaces that directly induced ALP aggregation. The results provide new information regarding ALP from M. rosenbergii.

Keywords: Alkaline phosphatase; Cu(2+); Inhibition kinetics.

MeSH terms

  • Alkaline Phosphatase / chemistry*
  • Alkaline Phosphatase / isolation & purification
  • Alkaline Phosphatase / metabolism*
  • Animals
  • Copper / chemistry*
  • Copper / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Ions / chemistry*
  • Kinetics
  • Molecular Conformation / drug effects
  • Palaemonidae / enzymology*
  • Protein Aggregates

Substances

  • Enzyme Inhibitors
  • Ions
  • Protein Aggregates
  • Copper
  • Alkaline Phosphatase