title: Catalysis of zinc transfer by D-penicillamine to secondary chelators.
abstract: 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.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Medical Scientist Training Program, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Chong
authors.forename: David S
authors.initials: DS
authors.lastname: Auld
mesh_terms: 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*
chemical_list: D002614:Chelating Agents; D004492:Edetic Acid; D004880:Ergothioneine; D043422:Carboxypeptidases A; D010396:Penicillamine; D015032:Zinc