Biosynthesis of the Iron-Molybdenum Cofactor of Nitrogenase

Yilin Hu,Markus W Ribbe

doi:10.1074/jbc.r113.454041

Abstract

The iron-molybdenum cofactor (the M-cluster) serves as the active site of molybdenum nitrogenase. Arguably one of the most complex metal cofactors in biological systems, the M-cluster is assembled through the formation of an 8Fe core prior to the insertion of molybdenum and homocitrate into this core. Here, we review the recent progress in the research area of M-cluster assembly, with an emphasis on our work that provides useful insights into the mechanistic details of this process.

Highlights

The structural complexity and biological importance of the M-cluster have prompted vigorous research on the assembly mechanism of this metal cofactor, as knowledge in this regard is important for understanding the structure-function relationship of nitrogenase but is instrumental in developing future synthetic strategies for nitrogenase-based biomimetic catalysts
It is believed that NifS, a pyridoxal phosphate-dependent cysteine desulfurase, forms a protein-bound cysteine persulfide, which is subsequently donated to NifU for the sequential formation of [Fe2S2] and [Fe4S4] units [11]
The K-cluster and the SAM motif-associated cluster give rise to an S ϭ 1/2 EPR signal at g ϭ 2.02, 1.95, and 1.90 [12]. This composite S ϭ 1/2 signal disappears upon addition of SAM, suggesting that the K-cluster and the SAM cluster are located in close proximity to each other [12]

Summary

Introduction

The structural complexity and biological importance of the M-cluster have prompted vigorous research on the assembly mechanism of this metal cofactor, as knowledge in this regard is important for understanding the structure-function relationship of nitrogenase but is instrumental in developing future synthetic strategies for nitrogenase-based biomimetic catalysts. Metal analysis further reveals the presence of additional [Fe4S4] clusters on NifB, which are associated with the conserved CxxxCxxC motifs (a characteristic feature of radical S-adenosyl-L-methionine (SAM)3 enzymes) in this protein [9].

Results

Conclusion