PROSITE documentation PDOC516564Fe-4S domain profile
The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is functional in the acetyl-CoA pathway of autotrophic carbon fixation in various bacteria and acrchaea, where it is essential for the biosynthesis of acetyl-CoA. CoFeSP acts in two methylation reactions: the transfer of a methyl group from methyltransferase (MeTr)-bound methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site cluster A of acetyl-CoA synthase (ACS). CoFeSP is a heterodimer consisting of a large subunit (CfsA) and a small subunit (CfsB). The large subunit has three domains: an amino (N)-terminal 4Fe-4S domain, a TIM barrel domain and a carboxy (C)-terminal domain that binds Coβ-aqua-(5,6-dimethylbenzimiddazolylcobamide) (corrinoid). Methylation of CoFeSP only occurs in the low potential Co(I) state, which can be sporadically oxidized to the inactive Co(II) state, making its reductive reactivation necessary. The low-potential [4Fe-4S]2(+)/1(+) cluster is involved in the reductive reactivation of CoFeSP and is able to transfer electrons to cob(II)amide from NiFe-containing carbon monoxyde dehydrogenase (CODH), pyruvate:ferredoxin oxydoreductase or reduced ferredoxins [1,2,3].
The 4Fe-4S domain lacks homology to the 4Fe-4S ferredoxin-type iron-sulfur binding domain (see <PDOC00176>), but is also found in bacterial electron transport complex protein RnfB [2].
The 4Fe-4S domain consists of four helices (three α-helices from H1-H3 and one 3(10)-helix with the order αH1-αH2-3(10)H-αH3) (see <PDB:2YCL>). This four-helix-bundle-like architecture positions the four cysteinyl ligands of the [4Fe-4S] cluster. The iron-sulfur cluster binding motif Cys-X(2)-Cys-X(4)-Cys-X(16)-Cys is located at loops connecting αH1 and αH2, connecting 3(10)H and αH3, and at the end of αH2. The [4Fe-4S] cluster is placed near the surface of the 4Fe-4S domain, but is shielded from the solvent by hydrophobic amino acids [2,3].
The profile we developed covers the entire 4Fe-4S domain.
Last update:August 2012 / New entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Svetlitchnaia T. Svetlitchnyi V. Meyer O. Dobbek H. |
| Title | Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 103:14331-14336(2006). | |
| PubMed ID | 16983091 | |
| DOI | 10.1073/pnas.0601420103 |
| 2 | Authors | Goetzl S. Jeoung J.-H. Hennig S.E. Dobbek H. |
| Title | Structural basis for electron and methyl-group transfer in a methyltransferase system operating in the reductive acetyl-CoA pathway. | |
| Source | J. Mol. Biol. 411:96-109(2011). | |
| PubMed ID | 21640123 | |
| DOI | 10.1016/j.jmb.2011.05.025 |
| 3 | Authors | Kung Y. Ando N. Doukov T.I. Blasiak L.C. Bender G. Seravalli J. Ragsdale S.W. Drennan C.L. |
| Title | Visualizing molecular juggling within a B12-dependent methyltransferase complex. | |
| Source | Nature 484:265-269(2012). | |
| PubMed ID | 22419154 | |
| DOI | 10.1038/nature10916 |
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