The requirement of inorganic Fe-S clusters for the biosynthesis of the organometallic molybdenum cofactor
- Iron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor (Moco). Here, we give an overview of the assembly of Fe-S clusters in bacteria and humans and present their connection to the Moco biosynthesis pathway. In all organisms, Fe-S cluster assembly starts with the abstraction of sulfur froml-cysteine and its transfer to a scaffold protein. After formation, Fe-S clusters are transferred to carrier proteins that insert them into recipient apo-proteins. In eukaryotes like humans and plants, Fe-S cluster assembly takes place both in mitochondria and in the cytosol. Both Moco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. Moco is a tricyclic pterin compound with molybdenum coordinated through its unique dithiolene group. Moco biosynthesis begins in theIron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor (Moco). Here, we give an overview of the assembly of Fe-S clusters in bacteria and humans and present their connection to the Moco biosynthesis pathway. In all organisms, Fe-S cluster assembly starts with the abstraction of sulfur froml-cysteine and its transfer to a scaffold protein. After formation, Fe-S clusters are transferred to carrier proteins that insert them into recipient apo-proteins. In eukaryotes like humans and plants, Fe-S cluster assembly takes place both in mitochondria and in the cytosol. Both Moco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. Moco is a tricyclic pterin compound with molybdenum coordinated through its unique dithiolene group. Moco biosynthesis begins in the mitochondria in a Fe-S cluster dependent step involving radical/S-adenosylmethionine (SAM) chemistry. An intermediate is transferred to the cytosol where the dithiolene group is formed, to which molybdenum is finally added. Further connections between Fe-S cluster assembly and Moco biosynthesis are discussed in detail.…
Author details: | Ralf R. MendelGND, Thomas W. HercherORCiD, Arkadiusz ZupokORCiDGND, Muhammad Abrar HasnatGND, Silke LeimkühlerORCiDGND |
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DOI: | https://doi.org/10.3390/inorganics8070043 |
ISSN: | 2304-6740 |
Title of parent work (English): | Inorganics : open access journal |
Publisher: | MDPI |
Place of publishing: | Basel |
Publication type: | Article |
Language: | English |
Date of first publication: | 2020/07/16 |
Publication year: | 2020 |
Release date: | 2023/03/23 |
Tag: | Fe-S cluster assembly; ISC; Moco biosynthesis; NIF; SUF; iron; l-cysteine desulfurase; molybdenum; sulfur |
Volume: | 8 |
Issue: | 7 |
Article number: | 43 |
Number of pages: | 23 |
Funding institution: | Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)German; Research Foundation (DFG) [LE1171/15-2, LE1171/11-2, ME1266/31-1]; DFGGerman Research Foundation (DFG)European Commission [SPP1927]; DFG; Research Training GroupGerman Research Foundation (DFG) [GRK 2223/1] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |
Publishing method: | Open Access / Gold Open-Access |
DOAJ gelistet | |
License (German): | CC-BY - Namensnennung 4.0 International |