On the Role of Additional [4Fe-4S] Clusters with a Free Coordination Site in Radical-SAM Enzymes.

Etienne Mulliez,Victor Duarte,Marc Fontecave,Mohamed Atta,Simon Arragain

doi:10.3389/fchem.2017.00017

Abstract

The canonical CysXXXCysXXCys motif is the hallmark of the Radical-SAM superfamily. This motif is responsible for the ligation of a [4Fe-4S] cluster containing a free coordination site available for SAM binding. The five enzymes MoaA, TYW1, MiaB, RimO and LipA contain in addition a second [4Fe-4S] cluster itself bound to three other cysteines and thus also displaying a potentially free coordination site. This review article summarizes recent important achievements obtained on these five enzymes with the main focus to delineate the role of this additional [4Fe-4S] cluster in catalysis.

Highlights

The amazing development of the Radical S-Adenosylmethionine (RS) enzymes is unique in the history of modern enzymology and covers three distinct periods
Co-substrate binding and activation lead us to propose and substantiate that the subsite iron in the additional cluster of MiaB and RimO could serve for the binding and delivery of a methylthio group during catalysis
The presence of an additional Fe-S cluster in the RS enzymes is historically connected to its discovery in BioB and Lipoyl synthase (LipA), the presently accepted mechanism of sulfur insertion brought about by the latter enzymes does not fit the one described in this review

Summary

Introduction

The amazing development of the Radical S-Adenosylmethionine (RS) enzymes is unique in the history of modern enzymology and covers three distinct periods. Both enzymes catalyze the same chemical reaction, namely, the transfer of a methylthio group on a specific adenine of several tRNAs for MiaB and on a specific aspartate residue in the ribosomal protein S12 (RPS12) for RimO and LipA which inserts two sulfur atoms in the octanoyl chain of several important 2-oxoacid dehydrogenases as well as of the glycine cleavage system to afford the essential growth factor lipoate.

Results

Conclusion