Catalysis of zinc transfer by D-penicillamine to secondary chelators.
The antiarthritis drug D-penicillamine (D-PEN) catalyzes zinc(II) transfer from carboxypeptidase A to chelators such as thionein and EDTA at a rate constant up to 400-fold faster than the uncatalyzed release. Once D-PEN releases zinc(II) from enzyme stronger chelators can tightly bind zinc(II) leading to complete and essentially irreversible inhibition. D-PEN is the first drug to inhibit a zinc protease by catalyzing metal removal, and the name "catalytic chelation" is proposed for this mechanism.
Chong
Curtis R
CR
Department of Pharmacology and Molecular Sciences, Medical Scientist Training Program, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Auld
David S
DS
D000818:Animals; D043422:Carboxypeptidases A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002384:Catalysis; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry*; D004357:Drug Synergism; D004492:Edetic Acid / Q000737:chemistry*; D004880:Ergothioneine / Q000737:chemistry*; D007700:Kinetics; D010396:Penicillamine / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D002614:Chelating Agents; D004492:Edetic Acid; D004880:Ergothioneine; D043422:Carboxypeptidases A; D010396:Penicillamine; D015032:Zinc