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Chemical arrows for enzymatic targets
Author(s) -
Colman Roberta F.
Publication year - 1997
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.11.4.9068610
Subject(s) - biochemistry , chemistry , allosteric regulation , enzyme , active site , affinity label , binding site , site directed mutagenesis , glutathione , affinity labeling , mutagenesis , stereochemistry , ligand (biochemistry) , receptor , mutation , mutant , gene
Reactive analogs of substrates or allosteric regulators can be designed to bind revers‐ibly to particular ligand sites of enzymes. Subsequently, these compounds can react cova‐lently with amino acids accessible from the ligand site, thereby functioning as chemical arrows aimed at specific enzymatic target sites. The approach of affinity labeling can be used to identify amino acid participants in active or regulatory sites, to provide a rational choice of targets for site‐directed mutagenesis experiments, or to monitor conformational changes in the region of a particular enzyme site. Illustrations of these approaches include: 1 ) the use of reactive nucleotide analogs directed to substrate sites in adenylosuccinate synthetase and adenylosuccinate lyase and to regulatory sites of glutamate dehydrogenase, 2 ) the use of affinity cleavage by Fe 2+ ‐isocitrate to locate the metal‐substrate site of isocitrate dehydrogenase, and 3) the use of reactive peptides and aromatic compounds to target the glutathione and xenobiotic sites of glutathione S ‐trans‐ferases.—Colman, R. F. Chemical arrows for enzymatic targets. FASEB J. 11, 217‐226 (1997)