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Changes in quaternary structure cause a kinetic asymmetry of glutamate racemase‐catalyzed homocysteic acid racemization
Author(s) -
Mackie Joanna,
Kumar Himank,
Bearne Stephen L.
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13248
Subject(s) - racemization , chemistry , stereochemistry , active site , substrate (aquarium) , bacillus subtilis , monomer , allosteric regulation , dimer , biochemistry , enzyme , organic chemistry , biology , bacteria , ecology , genetics , polymer
Glutamate racemases ( GR ) catalyze the racemization of d ‐ and l ‐glutamate and are targets for the development of antibiotics. We demonstrate that GR from the periodontal pathogen Fusobacterium nucleatum ( Fn GR ) catalyzes the racemization of d ‐homocysteic acid ( d ‐ HCA ), while l ‐ HCA is a poor substrate. This enantioselectivity arises because l ‐ HCA perturbs Fn GR 's monomer–dimer equilibrium toward inactive monomer. The inhibitory effect of l ‐ HCA may be overcome by increasing the total Fn GR concentration or by adding glutamate, but not by blocking access to the active site through site‐directed mutagenesis, suggesting that l ‐ HCA binds at an allosteric site. This phenomenon is also exhibited by GR from Bacillus subtilis , suggesting that enantiospecific, “substrate”‐induced dissociation of oligomers to form inactive monomers may furnish a new inhibition strategy.