Inhibition and Regulation of the Ergothioneine Biosynthetic Methyltransferase EgtD.

Ergothioneine is an emerging factor in cellular redox homeostasis in bacteria, fungi, plants, and animals. Reports that ergothioneine biosynthesis may be important for the pathogenicity of bacteria and fungi raise the question as to how this pathway is regulated and whether the corresponding enzymes may be therapeutic targets. The first step in ergothioneine biosynthesis is catalyzed by the methyltransferase EgtD that converts histidine into N-α-trimethylhistidine.

Structural aspects of thyroid hormone binding to proteins and competitive interactions with natural and synthetic compounds.

Thyroid hormones and their metabolites constitute a vast class of related iodothyronine compounds that contribute to the regulation of metabolic activity and cell differentiation. They are in turn transported, transformed and recognized as signaling molecules through binding to a variety of proteins from a wide range of evolutionary unrelated protein families, which renders these proteins and their iodothyronine binding sites an example for extensive convergent evolution. In this review, we will briefly summarize what is known about iodothyronine binding sites in proteins, the modes of protein/iodothyronine interaction, and the ligand conformations.

Structure of the Ergothioneine-Biosynthesis Amidohydrolase EgtC.

The ubiquitous sulfur metabolite ergothioneine is biosynthesized by oxidative attachment of a sulfur atom to the imidazole ring of Nα-trimethylhistidine. Most actinobacteria, including Mycobacterium tuberculosis, use γ-glutamyl cysteine as a sulfur donor. In subsequent steps the carbon scaffold of γ-glutamyl cysteine is removed by the glutamine amidohydrolase EgtC and the β-lyase EgtE.

Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway.

The non-heme iron enzyme EgtB catalyzes O2 -dependent C-S bond formation between γ-glutamyl cysteine and N-α-trimethyl histidine as the central step in ergothioneine biosynthesis. Both, the catalytic activity and the architecture of EgtB are distinct from known sulfur transferases or thiol dioxygenases. The crystal structure of EgtB from Mycobacterium thermoresistibile in complex with γ-glutamyl cysteine and N-α-trimethyl histidine reveals that the two substrates and three histidine residues serve as ligands in an octahedral iron binding site.

Ergothioneine biosynthetic methyltransferase EgtD reveals the structural basis of aromatic amino acid betaine biosynthesis.

Ergothioneine is an N-α-trimethyl-2-thiohistidine derivative that occurs in human, plant, fungal, and bacterial cells. Biosynthesis of this redox-active betaine starts with trimethylation of the α-amino group of histidine. The three consecutive methyl transfers are catalyzed by the S-adenosylmethionine-dependent methyltransferase EgtD.

Crystallization and preliminary X-ray analysis of the ergothioneine-biosynthetic methyltransferase EgtD.

Ergothioneine is an amino-acid betaine derivative of histidine that was discovered more than one century ago. Despite significant research pointing to a function in oxidative stress defence, the exact mechanisms of action of ergothioneine remain elusive. Although both humans and bacterial pathogens such as Mycobacterium tuberculosis seem to depend on ergothioneine, humans are devoid of the corresponding biosynthetic enzymes.

Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in other bacteria.

Background: The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity.