Structure of the <i>Escherichia coli</i> ThiS−ThiF Complex, a Key Component of the Sulfur Transfer System in Thiamin Biosynthesis<sup>,</sup>

Lehmann, Christopher; Begley, Tadhg P.; Ealick, S.E.

doi:10.1021/bi051502y

Cited by 97 publications

(92 citation statements)

References 43 publications

(57 reference statements)

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“…Another member of the family, TusE, has recently been shown to play a role in the biosynthesis of thiouridine at tRNA wobble positions with in vitro studies suggesting that the tail cysteine of TusE carries a sulfane group (29). The second distinct structural class of proteins that carry sulfur species on an external arm includes the MoaD protein involved in molybopterin cofactor biosynthesis (30) and the ThiS protein that participates in thiamine biosynthesis (31). These proteins have a 6-amino acid tail at the C terminus of the protein.…”

Section: Discussionmentioning

confidence: 99%

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

Sauvé

Bruno

Berks

et al. 2007

Journal of Biological Chemistry

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The bacterial Sox (sulfur oxidizing) system allows the utilization of inorganic sulfur compounds in energy metabolism. Central to this process is the SoxYZ complex that carries the pathway intermediates on a cysteine residue near the C terminus of SoxY. Crystal structures have been determined for Paracoccus pantotrophus SoxYZ with the carrier cysteine in the underivatized state, conjugated to the polysulfide mimic ␤-mercaptoethanol, and as the sulfonate adduct pathway intermediate. The carrier cysteine is located on a peptide swinging arm and is bracketed on either side by diglycine dipeptides acting as molecular universal joints. This structure provides a novel solution to the requirement that the cysteine-bound intermediates be able to access and orient themselves within the active sites of multiple partner enzymes. Adjacent to the swinging arm there is a conserved, deep, apolar pocket into which the ␤-mercaptoethanol adduct extends. This pocket would be well suited to a role in protecting labile pathway intermediates from adventitious reactions.

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Section: Discussionmentioning

confidence: 99%

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

Sauvé

Bruno

Berks

et al. 2007

Journal of Biological Chemistry

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“…46). The amino-acid sequence alignments of HcgE with its structural homologues, Schizoscaccharomyces pombe E1 ubiquitin-activating enzyme 47 , E. coli MoaB 22 , E. coli ThiF 48 and E. coli MccB 24 were also performed using the same method. HcgF structural homologues of Agrobacterium fabrum CinA (PDB code: 2A9S) and NMN deamidases, that is, E. coli YgaD, Shewanella oneidensis PncC 25 and Oceanobacillus iheyensis PncC 49 , were also aligned with HcgF from M. jannaschii using Clustal W2.…”

Section: Methodsmentioning

confidence: 99%

Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor

et al. 2015

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The iron-guanylylpyridinol (FeGP) cofactor of [Fe]-hydrogenase contains a prominent iron centre with an acyl-Fe bond and is the only acyl-organometallic iron compound found in nature. Here, we identify the functions of HcgE and HcgF, involved in the biosynthesis of the FeGP cofactor using structure-to-function strategy. Analysis of the HcgE and HcgF crystal structures with and without bound substrates suggest that HcgE catalyses the adenylylation of the carboxy group of guanylylpyridinol (GP) to afford AMP-GP, and subsequently HcgF catalyses the transesterification of AMP-GP to afford a Cys (HcgF)-S-GP thioester. Both enzymatic reactions are confirmed by in vitro assays. The structural data also offer plausible catalytic mechanisms. This strategy of thioester activation corresponds to that used for ubiquitin activation, a key event in the regulation of multiple cellular processes. It further implicates a nucleophilic attack onto the acyl carbon presumably via an electron-rich Fe(0)-or Fe(I)-carbonyl complex in the Fe-acyl formation.

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“…In the microcin system, Zn 2ϩ was originally proposed to serve as a Lewis acid, activating the amide carbonyl for cyclodehydration (22). Although that mechanism is certainly plausible, the crystal structures of ThiF, MoeB, and MccB have become available and show that the tertracysteine coordinated Zn 2ϩ is 20 Å away from the active site pocket where ATP binds (25,26). In addition to the CxxC motifs, the crystal structures of ThiF and MoeB resolved the amino acid residues critical for ATP binding.…”

Section: Closa-d Genetic Complementation Studies In Groupmentioning

confidence: 99%

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

Gonzalez

Lee

Hensler

et al. 2010

Journal of Biological Chemistry

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Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark ␤-hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S.Microbial virulence and survival are often defined by metabolic output. Among the many molecular species used to give a competitive advantage are hydrogen peroxide, genetically encoded small molecules, siderophores, proteins, and bacteriocins (1, 2). Streptolysin S (SLS) 2 is a well known hemolytic/ cytolytic, ribosomally encoded bacteriocin and virulence factor group A Streptococcus (GAS) (3)(4)(5). To this day, the characteristic ␤-hemolytic phenotype observed on blood agar plates is used as a clinical diagnostic tool for GAS identification. GAS is best known as the agent of acute pharyngitis (strep throat) but also may cause invasive infections, including necrotizing fasciitis and toxic shock syndrome. In the 100-year history of our knowledge of streptococcal bacteria, the precise chemical structure of this toxin has remained elusive, although the discovery of its biosynthetic gene cluster more than a decade ago (4) has guided investigations into its post-translational modification and likely heterocyclic nature (6, 7).Through recent comparative genomic analysis, an SLS-type gene cluster was identified in clostridia species including Clostridium botulinum and Clostridium sporogenes, two diseasecausing bacteria known to endanger food supplies (8 -10). Similar gene clusters were found in Staphylococcus aureus RF122, Bacillus thuringiensis, Streptococcus iniae, and Listeria monocytogenes 4b. The L. monocytogenes 4b strain is the primary serotype and causative agent for outbreaks of listeriosis (11). The S. aureus RF122 strain is responsible for bovine mastitis. S. iniae is a cytotoxic fish pathogen. This suggests that a shared metabolic output of these pathogens including SLS-like toxins may contribute to their pathogenic potential (11).Each of these SLS family gene clusters contains a similar set of genes. For instance, in C. botulinum and C. sporogenes, the closA-I genes are related by sequence to sagA-I from GAS (see Fig. 1A). Of these genes, ClosF is a protein of unknown function. ClosG, -H, and -I are ABC transporters and therefore are likely to be responsible for exporting the mature hemolytic product. ClosA is the prepropeptide (structural peptide) that is post-translationally modified to form the propeptide. ClosE has been annotated as an i...

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Structure of the Escherichia coli ThiS−ThiF Complex, a Key Component of the Sulfur Transfer System in Thiamin Biosynthesis^,

Cited by 97 publications

References 43 publications

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

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Structure of the Escherichia coli ThiS−ThiF Complex, a Key Component of the Sulfur Transfer System in Thiamin Biosynthesis,

Cited by 97 publications

References 43 publications

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

The SoxYZ Complex Carries Sulfur Cycle Intermediates on a Peptide Swinging Arm

Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

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Structure of the Escherichia coli ThiS−ThiF Complex, a Key Component of the Sulfur Transfer System in Thiamin Biosynthesis^,