Dual Role of the Molybdenum Cofactor Biosynthesis Protein MOCS3 in tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Humans

Chowdhury, Mita Mullick; Dosche, Carsten; Löhmannsröben, Hans‐Gerd; Leimkühler, Silke

doi:10.1074/jbc.m112.351429

Cited by 44 publications

(72 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MOCS3 was initially identified to be involved in molybdenum cofactor (Moco) biosynthesis in the cytosol (27). In this case, MOCS3 interacts with MOCS2A and forms a thiocarboxylate group at the C terminus of MOCS2A (24,25,27). MOCS2A subsequently assembles with MOCS2B to form the molybdopterin (MPT) synthase (28).…”

Section: Glnmentioning

confidence: 99%

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

Fräsdorf

Radon

Leimkühler

2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Localization and identification of interaction partners of two splice variants of the human 3-mercaptopyruvate sulfurtransferase TUM1. Results: We show that TUM1 interacts with proteins involved in Moco and FeS cluster biosynthesis. Conclusion: Human TUM1 is a dual localized protein in the cytosol and mitochondria with distinct roles in sulfur transfer and interaction partners. Significance: The study contributes to the sulfur transfer pathway for the biosynthesis of sulfur-containing biofactors.

show abstract

Section: Glnmentioning

confidence: 99%

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

Fräsdorf

Radon

Leimkühler

2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Crucially, MOCS3 is not only involved in Moco biosynthesis but also in the formation of thio-modified mcm 5 s 2 U34 nucleosides in tRNA for Gln, Glu and Lys in the cytosol of human cells (Chowdhury et al, 2012). To perform this shared function role in tRNA thiolation, MOCS3 interacts with the ubiquitin-related modifier protein1 (URM1) (Figure 4).…”

Section: Eukaryotic Mocs3 Is a Two-domain Protein With Multiple Intermentioning

confidence: 99%

“…After cleavage of the disulfide bond, thiocarboxylated URM1 is released. The sulfur of URM1-COSH is further transferred to mcm 5 U34 group of the tRNA Glu,Gln,Lys , aided by the CTU1 and CTU2 proteins under ATP consumption (Chowdhury et al, 2012).…”

Section: Eukaryotic Mocs3 Is a Two-domain Protein With Multiple Intermentioning

confidence: 99%

“…MOCS2B, thus, has a second role apart from Moco biosynthesis in humans, classifying it as a moonlighting protein. Further, MOCS3 is a fusion protein of a N-terminal MoeB-domain with homologies to ubiquitin-activating (Chowdhury et al, 2012). Further, the protein gephyrin is composed of two protein domains in humans, with a N-terminal MogA-like domain (G-domain) and a C-terminal MoeA-like domain (E-domain), which are connected by a long linker region (Tyagarajan and Fritschy, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Leimkühler

2017

Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Abstract:The biosynthesis of the molybdenum cofactor (Moco) is a highly conserved pathway in bacteria, archaea and eukaryotes. The molybdenum atom in Mococontaining enzymes is coordinated to the dithiolene group of a tricyclic pyranopterin monophosphate cofactor. The biosynthesis of Moco can be divided into three conserved steps, with a fourth present only in bacteria and archaea:(1) formation of cyclic pyranopterin monophosphate, (2) formation of molybdopterin (MPT), (3) insertion of molybdenum into MPT to form Mo-MPT, and (4) additional modification of Mo-MPT in bacteria with the attachment of a GMP or CMP nucleotide, forming the dinucleotide variants of Moco. While the proteins involved in the catalytic reaction of each step of Moco biosynthesis are highly conserved among the Phyla, a surprising link to other cellular pathways has been identified by recent discoveries. In particular, the pathways for FeS cluster assembly and thio-modifications of tRNA are connected to Moco biosynthesis by sharing the same protein components. Further, proteins involved in Moco biosynthesis are not only shared with other pathways, but additionally have moonlighting roles. This review gives an overview of Moco biosynthesis in bacteria and humans and highlights the shared function and moonlighting roles of the participating proteins.

show abstract

“…Since MOCS3 activity is also involved in tRNA thiolation and thereby in global processes like nuclear transport, cytokinesis and cell cycle progression one might, however, also speculate on a possible embryonal lethality as a consequence of hitherto not described MOCS3 mutations [24].…”

Section: Mocs3mentioning

confidence: 99%

Molybdenum Cofactor and Sulfite Oxidase Deficiency

Reiss¹

2016

Mol Biol (Los Angel)

View full text Add to dashboard Cite

A universal molybdenum-containing cofactor is necessary for the activity of all eukaryotic molybdoenzymes. In humans four such enzymes are known: Sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase and a mitochondrial amidoxime reducing component. Of these, sulfite oxidase is the most important and clinically relevant one. Mutations in the genes MOCS1, MOCS2 or GPHN -all encoding cofactor biosynthesis proteins -lead to molybdenum cofactor deficiency type A, B or C, respectively. All three types plus mutations in the SUOX gene responsible for isolated sulfite oxidase deficiency lead to progressive neurological disease which untreated in most cases leads to death in early childhood. Currently, only for type A of the cofactor deficiency an experimental treatment is available.

show abstract

Dual Role of the Molybdenum Cofactor Biosynthesis Protein MOCS3 in tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Humans

Cited by 44 publications

References 42 publications

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Molybdenum Cofactor and Sulfite Oxidase Deficiency

Contact Info

Product

Resources

About