Cooperativity induced by a single mutation at the subunit interface of a dimeric enzyme: glutathione reductase.
When glycine418 of Escherichia coli glutathione reductase, which is in a closely packed region of the dimer interface, is replaced with a bulky tryptophan residue, the enzyme becomes highly cooperative (Hill coefficient 1.76) for glutathione binding. The cooperativity is lost when the mutant subunit is hybridized with a wild-type subunit to create a heterodimer. The mutation appears to disrupt atomic packing at the dimer interface, which induces a change of kinetic mechanism. A single mutation in a region of the protein remote from the active site can thus act as a molecular switch to confer cooperativity on an enzyme.
Scrutton
N S
NS
Department of Biochemistry, University of Cambridge, United Kingdom.
Deonarain
M P
MP
Berry
A
A
Perham
R N
RN
D001483:Base Sequence; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005798:Genes, Bacterial; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D007700:Kinetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D009249:NADP / Q000378:metabolism; D010957:Plasmids; D055503:Protein Multimerization; D014364:Tryptophan / Q000737:chemistry
D046911:Macromolecular Substances; D009249:NADP; D014364:Tryptophan; D005980:Glutathione Reductase; D005978:Glutathione; D005998:Glycine