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Metal Ions as Cofactors for the Binding of Inhibitors to Methionine Aminopeptidase: A Critical View of the Relevance of In Vitro Metalloenzyme Assays
Author(s) -
Schiffmann Rolf,
Heine Andreas,
Klebe Gerhard,
Klein Christian D. P.
Publication year - 2005
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200500592
Subject(s) - in vitro , chemistry , cofactor , enzyme , metal , methionine , biochemistry , stereochemistry , aminopeptidase , metal ions in aqueous solution , organic chemistry , amino acid , leucine
Thiabendazole is a potent inhibitor of E. coli methionine aminopeptidase (MetAP) in vitro. Crystallographic structures of MetAP complexed with this and two other inhibitors show that binding is mediated by an auxiliary metal ion (see picture). This effect results from the high concentration of metal ions under in vitro conditions, and should be taken into account in assays for inhibitors of metal‐dependent enzymes.