Cooperativity induced by a single mutation at the subunit interface of a dimeric enzyme: glutathione reductase

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Science  13 Nov 1992:
Vol. 258, Issue 5085, pp. 1140-1143
DOI: 10.1126/science.1439821


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.