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• W2548652796 abstract "Negative cooperativity in enzyme reactions, in which the first event makes subsequent events less favorable, is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDGIC). However, the generality of this behavior across the divergent GST family and its evolutionary significance were unclear. To investigate, we studied 16 different GSTs, revealing that negative cooperativity is present only in more recently evolved GSTs, indicating evolutionary drift in this direction. In some variants, Hill coefficients were close to 0.5, the highest degree of negative cooperativity commonly observed (although smaller values of nH are theoretically possible). As DNDGIC is also a strong inhibitor of GSTs, we suggest negative cooperativity might have evolved to maintain a residual conjugating activity of GST against toxins even in the presence of high DNDGIC concentrations. Interestingly, two human isoenzymes that play a special protective role, safeguarding DNA from DNDGIC, display a classical half-of-the-sites interaction. Analysis of GST structures identified elements that could play a role in negative cooperativity in GSTs. Beside the well known lock-and-key and clasp motifs, other alternative structural interactions between subunits may be proposed for a few GSTs. Taken together, our findings suggest the evolution of self-preservation of enzyme function as a novel facility emerging from negative cooperativity. Negative cooperativity in enzyme reactions, in which the first event makes subsequent events less favorable, is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDGIC). However, the generality of this behavior across the divergent GST family and its evolutionary significance were unclear. To investigate, we studied 16 different GSTs, revealing that negative cooperativity is present only in more recently evolved GSTs, indicating evolutionary drift in this direction. In some variants, Hill coefficients were close to 0.5, the highest degree of negative cooperativity commonly observed (although smaller values of nH are theoretically possible). As DNDGIC is also a strong inhibitor of GSTs, we suggest negative cooperativity might have evolved to maintain a residual conjugating activity of GST against toxins even in the presence of high DNDGIC concentrations. Interestingly, two human isoenzymes that play a special protective role, safeguarding DNA from DNDGIC, display a classical half-of-the-sites interaction. Analysis of GST structures identified elements that could play a role in negative cooperativity in GSTs. Beside the well known lock-and-key and clasp motifs, other alternative structural interactions between subunits may be proposed for a few GSTs. Taken together, our findings suggest the evolution of self-preservation of enzyme function as a novel facility emerging from negative cooperativity." @default.
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• W2548652796 date "2016-12-01" @default.
• W2548652796 modified "2023-09-30" @default.
• W2548652796 title "Evolution of Negative Cooperativity in Glutathione Transferase Enabled Preservation of Enzyme Function" @default.
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• W2548652796 cites W1699618747 @default.
• W2548652796 cites W172254742 @default.
• W2548652796 cites W1868880553 @default.
• W2548652796 cites W1965064962 @default.
• W2548652796 cites W1966530947 @default.
• W2548652796 cites W1973910453 @default.
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• W2548652796 cites W1978790337 @default.
• W2548652796 cites W1979702489 @default.
• W2548652796 cites W1980535086 @default.
• W2548652796 cites W1981367433 @default.
• W2548652796 cites W1984443050 @default.
• W2548652796 cites W1984883228 @default.
• W2548652796 cites W1986552258 @default.
• W2548652796 cites W1993214140 @default.
• W2548652796 cites W1998093640 @default.
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• W2548652796 cites W2078952222 @default.
• W2548652796 cites W2079178286 @default.
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• W2548652796 cites W2082279195 @default.
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• W2548652796 doi "https://doi.org/10.1074/jbc.m116.749507" @default.
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