TY  - JOUR
A1  - Mendel, Ralf R.
A1  - Hercher, Thomas W.
A1  - Zupok, Arkadiusz
A1  - Hasnat, Muhammad Abrar
A1  - Leimkühler, Silke
T1  - The requirement of inorganic Fe-S clusters for the biosynthesis of the organometallic molybdenum cofactor
JF  - Inorganics : open access journal
N2  - 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 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.
KW  - Moco biosynthesis
KW  - Fe-S cluster assembly
KW  - l-cysteine desulfurase
KW  - ISC
KW  - SUF
KW  - NIF
KW  - iron
KW  - molybdenum
KW  - sulfur
Y1  - 2020
U6  - https://doi.org/10.3390/inorganics8070043
SN  - 2304-6740
VL  - 8
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Leimkühler, Silke
A1  - Bühning, Martin
A1  - Beilschmidt, Lena
T1  - Shared sulfur mobilization routes for tRNA thiolation and molybdenum cofactor biosynthesis in prokaryotes and eukaryotes
JF  - Biomolecules
N2  - Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm(5)s(2)U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure. The trafficking and delivery of sulfur nucleosides is a complex process carried out by sulfur relay systems involving numerous proteins, which not only deliver sulfur to the specific tRNAs but also to other sulfur-containing molecules including iron-sulfur clusters, thiamin, biotin, lipoic acid and molybdopterin (MPT). Among the biosynthesis of these sulfur-containing molecules, the biosynthesis of the molybdenum cofactor (Moco) and the synthesis of thio-modified tRNAs in particular show a surprising link by sharing protein components for sulfur mobilization in pro- and eukaryotes.
KW  - tRNA
KW  - molybdenum cofactor
KW  - persulfide
KW  - thiocarboxylate
KW  - thionucleosides
KW  - sulfurtransferase
KW  - l-cysteine desulfurase
Y1  - 2017
U6  - https://doi.org/10.3390/biom7010005
SN  - 2218-273X
VL  - 7
IS  - 1
PB  - MDPI
CY  - Basel
ER  -