[4Fe-4S]-dependent radical S-adenosylmethionine(SAM)proteins are a superfamily of oxidoreductases that can catalyze a series of challenging transformations using the common 5-d Ado radical intermediate.Although the st...[4Fe-4S]-dependent radical S-adenosylmethionine(SAM)proteins are a superfamily of oxidoreductases that can catalyze a series of challenging transformations using the common 5-d Ado radical intermediate.Although the structures and functions of radical SAM enzymes have been extensively studied,the electronic state-dependent reactions of the[4Fe-4S]clusters in these enzymes are still elusive.Herein we performed QM/MM calculations to elucidate the electronic state-dependent reactivity of the[4Fe-4S]cluster in pyruvate-formate lyase activating enzyme.Our calculations show that the electronic statedependent SAM activation by the[4Fe-4S]clusters in radical SAM enzyme is determined by both the super-exchange and exchange-enhanced reactivities.The super-exchange coupling in the[4Fe-4S]cluster favors the antiferromagnetic coupling between two neighbouring pairs,which results in theα-electron rather than theβ-electron donation from the[4Fe-4S]^(1+)cluster toward the SAM activation.Meanwhile,in the most favorable electronic state for the reductive cleavage of S-C5′,Fe4 would donate itsα-electron to gain the maximum exchange interactions in the Fe4-block.Such super-exchange and exchange-enhanced reactivity could be the general principles for reactivities of[4Fe-4S]cluster in RS enzymes.展开更多
基金supported by the National Natural Science Foundation of China (No.22073077, No.21933009,and No.21907082)
文摘[4Fe-4S]-dependent radical S-adenosylmethionine(SAM)proteins are a superfamily of oxidoreductases that can catalyze a series of challenging transformations using the common 5-d Ado radical intermediate.Although the structures and functions of radical SAM enzymes have been extensively studied,the electronic state-dependent reactions of the[4Fe-4S]clusters in these enzymes are still elusive.Herein we performed QM/MM calculations to elucidate the electronic state-dependent reactivity of the[4Fe-4S]cluster in pyruvate-formate lyase activating enzyme.Our calculations show that the electronic statedependent SAM activation by the[4Fe-4S]clusters in radical SAM enzyme is determined by both the super-exchange and exchange-enhanced reactivities.The super-exchange coupling in the[4Fe-4S]cluster favors the antiferromagnetic coupling between two neighbouring pairs,which results in theα-electron rather than theβ-electron donation from the[4Fe-4S]^(1+)cluster toward the SAM activation.Meanwhile,in the most favorable electronic state for the reductive cleavage of S-C5′,Fe4 would donate itsα-electron to gain the maximum exchange interactions in the Fe4-block.Such super-exchange and exchange-enhanced reactivity could be the general principles for reactivities of[4Fe-4S]cluster in RS enzymes.
