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.
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