Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB–MoaD complex

  title={Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB–MoaD complex},
  author={Michael W. Lake and Margot M. Wuebbens and Krishnan Rajagopalan and Hermann Schindelin},
The activation of ubiquitin and related protein modifiers is catalysed by members of the E1 enzyme family that use ATP for the covalent self-attachment of the modifiers to a conserved cysteine. The Escherichia coli proteins MoeB and MoaD are involved in molybdenum cofactor (Moco) biosynthesis, an evolutionarily conserved pathway. The MoeB- and E1-catalysed reactions are mechanistically similar, and despite a lack of sequence similarity, MoaD and ubiquitin display the same fold including a… 

The sulfurtransferase activity of Uba4 presents a link between ubiquitin-like protein conjugation and activation of sulfur carrier proteins.

The functional similarities between Uba4 and MOCS3 further demonstrate the evolutionary link between ATP-dependent protein conjugation and ATP- dependent cofactor sulfuration.

IscS Functions as a Primary Sulfur-donating Enzyme by Interacting Specifically with MoeB and MoaD in the Biosynthesis of Molybdopterin in Escherichia coli*

It is demonstrated by surface plasmon resonance analyses that IscS is the primary physiological sulfur-donating enzyme for the generation of the thiocarboxylate of MPT synthase in MPT biosynthesis.

Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans.

In a defined in vitro system for the generation of MPT from precursor Z, the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of M OCS2A, the small MPT synthase subunit in humans.

Crystal Structure of the Human Ubiquitin-activating Enzyme 5 (UBA5) Bound to ATP

Structural features are determined that further the understanding of the UBA5 enzyme reaction mechanism and provide insight into the evolution of ubiquitin activation.

The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains

BackgroundUbiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation

E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea

A working model for archaea is proposed in which the E1-like UbaA can activate multiple Ubl SAMPs for protein conjugation as well as for sulfur transfer, and a fundamental insight is provided into the diverse cellular functions of the Ubl system.

A Novel Role for Human Nfs1 in the Cytoplasm

The results suggest that cytosolic Nfs1 has an important role in sulfur transfer for the biosynthesis of Moc, the last step of molybdenum cofactor (Moco) biosynthesis in eukaryotes.

Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8

The structure and mutational analysis of human APPBP1–UBA3, the heterodimeric E1 enzyme for NEDD8, is reported here.

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

An overview of Moco biosynthesis in bacteria and humans is given and the shared function and moonlighting roles of the participating proteins are highlighted.



Characterization of Escherichia coli MoeB and Its Involvement in the Activation of Molybdopterin Synthase for the Biosynthesis of the Molybdenum Cofactor*

Using purified proteins, it is demonstrated the ATP-dependent formation of a complex of MoeB and MoaD adenylate that is stable to gel filtration.

Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation

The strong structural similarity between the small subunit of MPT synthase and ubiquitin provides evidence for the evolutionary antecedence of the Moco biosynthetic pathway to the Ubiquitin dependent protein degradation pathway.

Glycyl-tRNA synthetase uses a negatively charged pit for specific recognition and activation of glycine.

GlyRS utilizes the same general mechanism as that employed by other class II aminoacyl-tRNA synthetases, and uses class II-conserved residues to interact with the ATP and the adenosine-phosphate moiety of glycyl-adenylate.

Site-directed mutagenesis of ubiquitin. Differential roles for arginine in the interaction with ubiquitin-activating enzyme.

The four arginines present on ubiquitin at positions 42, 54, 72, and 74 were independently mutated to leucine and their effects on the interaction of the resulting polypeptides with ubiquit in-activating enzyme (E1) were characterized.

A Sulfurtransferase Is Required in the Transfer of Cysteine Sulfur in the in Vitro Synthesis of Molybdopterin from Precursor Z in Escherichia coli *

It was found that MPT can be produced from precursor Z in an E. coli iscS mutant strain, indicating that IscS is not required for the in vivo sulfuration of MPT synthase, and a comparison of the ability of the three sulfurtransferases to provide the sulfur for MPT formation showed the highest activity for CSD in the in vitro system.

Evidence That ThiI, an Enzyme Shared between Thiamin and 4-Thiouridine Biosynthesis, May Be a Sulfurtransferase That Proceeds through a Persulfide Intermediate*

It is concluded that Cys-456 of ThiI is critical for activity and a general mechanism for sulfur transfer in which the terminal sulfur of the persulfide first acts as a nucleophile and is then transferred as an equivalent of S2− rather than S0.

Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: Identification of an acyldisulfide-linked protein–protein conjugate that is functionally analogous to the ubiquitin/E1 complex

This ThiF/ThiS conjugate is the first characterized example of a unique acyldisulfide intermediate in a biosynthetic system and supports a strong evolutionary link between thiamin biosynthesis and the ubiquitin conjugating system.

Biosynthesis and processing of the molybdenum cofactors.

To each other, and define an electron-transfer pathway, which may explain the strong substrate inhibition observed in Mop [S] as well as in xanthine oxidase.

Evolution and function of ubiquitin-like protein-conjugation systems

Newly discovered parallels between the activation of ubiquitin and the biosynthesis of certain enzyme cofactors now hint at the possible evolutionary origins of the Ubiquitin system.