{PDOC51656} {PS51656; 4FE4S} {BEGIN} ************************* * 4Fe-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 CoBeta-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 ), but is also found in bacterial electron transport complex protein RnfB [2]. The 4Fe-4S domain consists of four helices (three alpha-helices from H1-H3 and one 3(10)-helix with the order alphaH1-alphaH2-3(10)H-alphaH3) (see ). 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 alphaH1 and alphaH2, connecting 3(10)H and alphaH3, and at the end of alphaH2. 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2012 / New entry. [ 1] Svetlitchnaia T., Svetlitchnyi V., Meyer O., Dobbek H. "Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis." Proc. Natl. Acad. Sci. U.S.A. 103:14331-14336(2006). PubMed=16983091; DOI=10.1073/pnas.0601420103 [ 2] Goetzl S., Jeoung J.-H., Hennig S.E., Dobbek H. "Structural basis for electron and methyl-group transfer in a methyltransferase system operating in the reductive acetyl-CoA pathway." J. Mol. Biol. 411:96-109(2011). PubMed=21640123; DOI=10.1016/j.jmb.2011.05.025 [ 3] Kung Y., Ando N., Doukov T.I., Blasiak L.C., Bender G., Seravalli J., Ragsdale S.W., Drennan C.L. "Visualizing molecular juggling within a B12-dependent methyltransferase complex." Nature 484:265-269(2012). PubMed=22419154; DOI=10.1038/nature10916 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}