The functional role of zinc in angiotensin converting enzyme: implications for the enzyme mechanism

J Inorg Biochem. 1985 Jul;24(3):183-98. doi: 10.1016/0162-0134(85)85002-9.

Abstract

Zinc is essential to the catalytic activity of angiotensin converting enzyme. The enzyme contains one g-atom of zinc per mole of protein. Chelating agents abolish activity by removing the metal ion to yield the inactive, metal-free apoenzyme. Zinc does not stabilize protein structure since the native and apoenzymes are equally susceptible to heat denaturation. Addition of either Zn2+, Co2+, or Mn2+ to the apoenzyme generates an active metalloenzyme; Fe2+, Ni2+, Cu2+, Cd2+, and Hg2+ fail to restore activity. The activities of the metalloenzymes follow the order Zn greater than Co greater than Mn. The protein binds Zn2+ more firmly than it does Co2+ or Mn2+. Hydrolysis of the chromophoric substrate, furanacryloyl-Phe-Gly-Gly, by the active metalloenzymes is subject to chloride activation; the activation constant is not metal dependent. Metal replacement mainly affects Kcat with very little change in Km, indicating that the role of zinc is to catalyze peptide hydrolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoenzymes / isolation & purification
  • Cross-Linking Reagents / pharmacology
  • Edetic Acid / pharmacology
  • Egtazic Acid / pharmacology
  • Kinetics
  • Lung / enzymology
  • Peptidyl-Dipeptidase A / metabolism*
  • Phenanthrolines / pharmacology
  • Rabbits
  • Zinc / analysis
  • Zinc / metabolism*

Substances

  • Apoenzymes
  • Cross-Linking Reagents
  • Phenanthrolines
  • Egtazic Acid
  • Edetic Acid
  • Peptidyl-Dipeptidase A
  • Zinc
  • 1,10-phenanthroline