Enzymes that contain iron-sulfur clusters participate in diverse and essential cellular processes such as electron transfer and nitrogen fixation. In the cube-shaped [4Fe-4S] cluster, the iron atoms exist as mixed valence Fe(II)/Fe(III) pairs, and the sulfur atoms are in the sulfide (S2-) oxidation state. The fact that both Fe2+ and S2- are metabolically toxic has led to the appreciation that assembly of this cluster likely involves multiple oxidation-reduction steps.
Krebs et al., working on the nitrogen-fixing (Nif) system in Azotobacter vinelandii, show that sulfane sulfur (S0), which is produced by the cysteine desulfurase NifS, is combined with ferrous ion (Fe2+) to build first a [2Fe-2S] cluster and then a [4Fe-4S] cluster, which can be inserted into an apoenzyme. Assembly takes place on a dimeric protein designated NifIscA, which is the homolog of Escherichia coli IscA (iron-sulfur cluster), and these authors propose that sulfur reduction is coupled to iron oxidation. This use of NifIscA as a construction scaffold is reminiscent of the interaction between IscS, a cysteine desulfurase and the E. coli homolog of NifS, and IscU, the homolog of NifU. Smith et al. and Urbina et al. have shown that sulfane sulfur is transferred directly from the active site of IscS to cysteine residues of IscU in a parallel pathway for making [Fe-S] clusters. What distinguishes the scaffolding roles of IscA and IscU is not yet clear, but recent work by Schwartz et al. has revealed that the gene cluster iscSUA is regulated by the product of an upstream open reading frame iscR; the IscR protein itself binds a [2Fe-2S] cluster. -- GJC
Biochemistry 40, 14069 (2001); J. Am. Chem. Soc. 123, 11103 (2001); J. Biol. Chem. 276, 44521 (2001); Proc. Natl. Acad. Sci. U.S.A. 98, 14895 (2001).
