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 (...
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MDPI AG
2020-07-01
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| Series: | Inorganics |
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| Online Access: | https://www.mdpi.com/2304-6740/8/7/43 |
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| author | Ralf R. Mendel Thomas W. Hercher Arkadiusz Zupok Muhammad A. Hasnat Silke Leimkühler |
| author_facet | Ralf R. Mendel Thomas W. Hercher Arkadiusz Zupok Muhammad A. Hasnat Silke Leimkühler |
| author_sort | Ralf R. Mendel |
| collection | DOAJ |
| description | 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 from <span style="font-variant: small-caps;">l</span>-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. |
| first_indexed | 2024-03-10T18:27:28Z |
| format | Article |
| id | doaj.art-3aab62d4281c4195838b2215372ced61 |
| institution | Directory Open Access Journal |
| issn | 2304-6740 |
| language | English |
| last_indexed | 2024-03-10T18:27:28Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Inorganics |
| spelling | doaj.art-3aab62d4281c4195838b2215372ced612023-11-20T06:54:59ZengMDPI AGInorganics2304-67402020-07-01874310.3390/inorganics8070043The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum CofactorRalf R. Mendel0Thomas W. Hercher1Arkadiusz Zupok2Muhammad A. Hasnat3Silke Leimkühler4Institute of Plant Biology, Braunschweig University of Technology, Humboldtstr. 1, 38106 Braunschweig, GermanyInstitute of Plant Biology, Braunschweig University of Technology, Humboldtstr. 1, 38106 Braunschweig, GermanyDepartment of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, GermanyDepartment of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, GermanyDepartment of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, GermanyIron-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 from <span style="font-variant: small-caps;">l</span>-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.https://www.mdpi.com/2304-6740/8/7/43Moco biosynthesisFe-S cluster assembly<span style="font-variant: small-caps">l</span>-cysteine desulfuraseISCSUFNIF |
| spellingShingle | Ralf R. Mendel Thomas W. Hercher Arkadiusz Zupok Muhammad A. Hasnat Silke Leimkühler The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor Inorganics Moco biosynthesis Fe-S cluster assembly <span style="font-variant: small-caps">l</span>-cysteine desulfurase ISC SUF NIF |
| title | The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor |
| title_full | The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor |
| title_fullStr | The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor |
| title_full_unstemmed | The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor |
| title_short | The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor |
| title_sort | requirement of inorganic fe s clusters for the biosynthesis of the organometallic molybdenum cofactor |
| topic | Moco biosynthesis Fe-S cluster assembly <span style="font-variant: small-caps">l</span>-cysteine desulfurase ISC SUF NIF |
| url | https://www.mdpi.com/2304-6740/8/7/43 |
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