scholarly journals The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor

Inorganics ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 43
Author(s):  
Ralf R. Mendel ◽  
Thomas W. Hercher ◽  
Arkadiusz Zupok ◽  
Muhammad A. Hasnat ◽  
Silke Leimkühler
Keyword(s):  
Electron Transfer ◽  
Scaffold Protein ◽  
Molybdenum Cofactor ◽  
Cluster Assembly ◽  
Biosynthesis Pathway ◽  
Carrier Proteins ◽  
Essential Protein ◽  
Iron Sulfur ◽  
Prosthetic Groups

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 l-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.

scholarly journals The Role of CyaY in Iron Sulfur Cluster Assembly on the E. coli IscU Scaffold Protein

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e21992 ◽  
Author(s):  
Clara Iannuzzi ◽  
Salvatore Adinolfi ◽  
Barry D. Howes ◽  
Ricardo Garcia-Serres ◽  
Martin Clémancey ◽  
...  
Keyword(s):  
Scaffold Protein ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
E Coli ◽  
Iron Sulfur

scholarly journals Physical and Functional Interactions of a Monothiol Glutaredoxin and an Iron Sulfur Cluster Carrier Protein with the Sulfur-donating Radical S-Adenosyl-l-methionine Enzyme MiaB

2013 ◽  
Vol 288 (20) ◽  
pp. 14200-14211 ◽  
Author(s):  
Sylvain Boutigny ◽  
Avneesh Saini ◽  
Edward E. K. Baidoo ◽  
Natasha Yeung ◽  
Jay D. Keasling ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Carrier Protein ◽  
Cluster Assembly ◽  
Carrier Proteins ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Initial Cluster ◽  
Initial Assembly

The biosynthesis of iron sulfur (FeS) clusters, their trafficking from initial assembly on scaffold proteins via carrier proteins to final incorporation into FeS apoproteins, is a highly coordinated process enabled by multiprotein systems encoded in iscRSUAhscBAfdx and sufABCDSE operons in Escherichia coli. Although these systems are believed to encode all factors required for initial cluster assembly and transfer to FeS carrier proteins, accessory factors such as monothiol glutaredoxin, GrxD, and the FeS carrier protein NfuA are located outside of these defined systems. These factors have been suggested to function both as shuttle proteins acting to transfer clusters between scaffold and carrier proteins and in the final stages of FeS protein assembly by transferring clusters to client FeS apoproteins. Here we implicate both of these factors in client protein interactions. We demonstrate specific interactions between GrxD, NfuA, and the methylthiolase MiaB, a radical S-adenosyl-l-methionine-dependent enzyme involved in the maturation of a subset of tRNAs. We show that GrxD and NfuA physically interact with MiaB with affinities compatible with an in vivo function. We furthermore demonstrate that NfuA is able to transfer its cluster in vitro to MiaB, whereas GrxD is unable to do so. The relevance of these interactions was demonstrated by linking the activity of MiaB with GrxD and NfuA in vivo. We observe a severe defect in in vivo MiaB activity in cells lacking both GrxD and NfuA, suggesting that these proteins could play complementary roles in maturation and repair of MiaB.

Structural and functional characterization of an iron–sulfur cluster assembly scaffold protein-SufA from Plasmodium vivax

Gene ◽  
2016 ◽  
Vol 585 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Zarna Rajeshkumar Pala ◽  
Vishal Saxena ◽  
Gagandeep Singh Saggu ◽  
Sushil Kumar Yadav ◽  
R.P. Pareek ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Functional Characterization ◽  
Scaffold Protein ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur

scholarly journals Archaeal ApbC/Nbp35 Homologs Function as Iron-Sulfur Cluster Carrier Proteins

2008 ◽  
Vol 191 (5) ◽  
pp. 1490-1497 ◽  
Author(s):  
Jeffrey M. Boyd ◽  
Randy M. Drevland ◽  
Diana M. Downs ◽  
David E. Graham
Keyword(s):  
Genetic System ◽  
Growth Defect ◽  
Cluster Assembly ◽  
Carrier Proteins ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Amino Terminal ◽  
Iron Sulfur ◽  
Major Cluster

ABSTRACT Iron-sulfur clusters may have been the earliest catalytic cofactors on earth, and most modern organisms use them extensively. Although members of the Archaea produce numerous iron-sulfur proteins, the major cluster assembly proteins found in the Bacteria and Eukarya are not universally conserved in archaea. Free-living archaea do have homologs of the bacterial apbC and eukaryotic NBP35 genes that encode iron-sulfur cluster carrier proteins. This study exploits the genetic system of Salmonella enterica to examine the in vivo functionality of apbC/NBP35 homologs from three archaea: Methanococcus maripaludis, Methanocaldococcus jannaschii, and Sulfolobus solfataricus. All three archaeal homologs could correct the tricarballylate growth defect of an S. enterica apbC mutant. Additional genetic studies showed that the conserved Walker box serine and the Cys-X-X-Cys motif of the M. maripaludis MMP0704 protein were both required for function in vivo but that the amino-terminal ferredoxin domain was not. MMP0704 protein and an MMP0704 variant protein missing the N-terminal ferredoxin domain were purified, and the Fe-S clusters were chemically reconstituted. Both proteins bound equimolar concentrations of Fe and S and had UV-visible spectra similar to those of known [4Fe-4S] cluster-containing proteins. This family of dimeric iron-sulfur carrier proteins evolved before the archaeal and eukaryal lineages diverged, representing an ancient mode of cluster assembly.

scholarly journals Structure and Dynamics of the Iron−Sulfur Cluster Assembly Scaffold Protein IscU and Its Interaction with the Cochaperone HscB

Biochemistry ◽  
2009 ◽  
Vol 48 (26) ◽  
pp. 6062-6071 ◽  
Author(s):  
Jin Hae Kim ◽  
Anna K. Füzéry ◽  
Marco Tonelli ◽  
Dennis T. Ta ◽  
William M. Westler ◽  
...  
Keyword(s):  
Scaffold Protein ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Structure And Dynamics ◽  
Iron Sulfur

scholarly journals A missed Fe-S cluster handoff causes a metabolic shakeup

2018 ◽  
Vol 293 (21) ◽  
pp. 8312-8313 ◽  
Author(s):  
Olivier Berteau
Keyword(s):  
Human Disease ◽  
Lipid Droplets ◽  
General Framework ◽  
Scaffold Protein ◽  
Cellular System ◽  
Metabolic Reprogramming ◽  
Cluster Assembly ◽  
Iron Sulfur ◽  
Pathological Conditions ◽  
In Cells

The general framework of pathways by which iron–sulfur (Fe-S) clusters are assembled in cells is well-known, but the cellular consequences of disruptions to that framework are not fully understood. Crooks et al. report a novel cellular system that creates an acute Fe-S cluster deficiency, using mutants of ISCU, the main scaffold protein for Fe-S cluster assembly. Surprisingly, the resultant metabolic reprogramming leads to the accumulation of lipid droplets, a situation encountered in many poorly understood pathological conditions, highlighting unanticipated links between Fe-S assembly machinery and human disease.

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