Small-molecule inhibitor: EDTA

Summary Literature Inhibits

Name

Common name
EDTA
Other names
edetic acid; ethylenediaminetetraacetic acid

Inhibition

History
As a well known chelating agent, the ability of EDTA to inhibit metal-dependent enzymes has long been known.
Peptidases inhibited
Most metallopeptidases are inhibited, as are calcium-dependent cysteine peptidases including the calpains in family C2 and clostripain in family C11 (Mitchell & Harrington, 1970).
Mechanism
Inhibition of a metallopeptidase normally results from removal of the metal ion (commonly zinc). The metal ion may be very tightly bound to the enzyme, with a long half-time for dissociation, in which case inhibition by EDTA may be so slow as to be undetectable (Auld, 1995). If the metal-free apoenzyme is stable, it can be reactivated by micromolar concentrations of appropriate metal ions; higher concentrations may be inhibitory (Larsen & Auld, 1991).
DrugBank
DB00974

Chemistry

CID at PubChem
6049
ChEBI
42191
Structure
[EDTA (M04.001 inhibitor) structure ]
Chemical/biochemical name
2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid
Formula weight
292

General

Inhibitor class
This compound is of the metal chelator class. Metal chelators contain anionic or neutral oxygen, nitrogen or sulfur atoms spatially arranged so as to give bi-, tri- or tetradentate ligation to a metal atom. Chelators can inhibit metalloenzymes either by removal of the metal from the enzyme or by binding to it to form a ternary complex (Auld, 1995).
Comment
1,10-Phenanthroline (q.v.) is much more selective than EDTA for the chelation of zinc over calcium ions, and is therefore more appropriate as a diagnostic reagent for a metallopeptidase (Salvesen & Nagase, 2001).
Reviews
Auld (1988)