The functional role of zinc in angiotensin converting enzyme: implications for the enzyme mechanism.
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.
D000818:Animals; D001051:Apoenzymes / Q000302:isolation & purification; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D011817:Rabbits; D015032:Zinc / Q000032:analysis / Q000378:metabolism*
D001051:Apoenzymes; D003432:Cross-Linking Reagents; D010618:Phenanthrolines; D004533:Egtazic Acid; D004492:Edetic Acid; D007703:Peptidyl-Dipeptidase A; D015032:Zinc; C025205:1,10-phenanthroline