A Different Look for AB5 Toxins

Gomis‐Rüth, F. Xavier

doi:10.1016/j.str.2013.10.004

Cited by 8 publications

(7 citation statements)

References 13 publications

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“…These are virulence factors of pathogenic bacteria that consist of a pentameric B subunit for host‐cell invasion and an A subunit that subverts intracellular functions . In contrast to previously studied related toxins, EcxAB from E. coli and CfxAB from Citrobacter freundii exhibit the metzincin consensus sequence within their A subunits, and the crystal structure of the former reveals that they fulfill the structural requirements for a novel metzincin family, the toxilysins . The structure of EcxA, the only one reported to date for the family (Table ), is a compact disk of 258 residues (Figs.…”

Section: Metzincin Family‐specific Featuresmentioning

confidence: 99%

Architecture and function of metallopeptidase catalytic domains

2013

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The cleavage of peptide bonds by metallopeptidases (MPs) is essential for life. These ubiquitous enzymes participate in all major physiological processes, and so their deregulation leads to diseases ranging from cancer and metastasis, inflammation, and microbial infection to neurological insults and cardiovascular disorders. MPs cleave their substrates without a covalent intermediate in a singlestep reaction involving a solvent molecule, a general base/acid, and a mono-or dinuclear catalytic metal site. Most monometallic MPs comprise a short metal-binding motif (HEXXH), which includes two metalbinding histidines and a general base/acid glutamate, and they are grouped into the zincin tribe of MPs. The latter divides mainly into the gluzincin and metzincin clans. Metzincins consist of globular~130-270-residue catalytic domains, which are usually preceded by N-terminal pro-segments, typically required for folding and latency maintenance. The catalytic domains are often followed by C-terminal domains for substrate recognition and other protein-protein interactions, anchoring to membranes, oligomerization, and compartmentalization. Metzincin catalytic domains consist of a structurally conserved N-terminal subdomain spanning a five-stranded b-sheet, a backing helix, and an active-site helix. The latter contains most of the metal-binding motif, which is here characteristically extended to HEXXHXXGXX(H,D). Downstream C-terminal subdomains are generally shorter, differ more among metzincins, and mainly share a conserved loop-the Met-turn-and a C-terminal helix. The accumulated structural data from more than 300 deposited structures of the 12 currently characterized metzincin families reviewed here provide detailed knowledge of the molecular features of their catalytic domains, help in our understanding of their working mechanisms, and form the basis for the design of novel drugs.Keywords: structural biochemistry; metzincin clan; catalytic domains; active-site cleft; hydrolytic enzymes; matrix metalloproteases; astacins; ADAM; adamalysins; serralysins; metalloprotease; metalloproteinase PeptidasesThe term "peptidase" is currently recommended for proteolytic enzymes, proteases, and proteinases in general.1 Peptidases are distributed among all kingdoms of life. 2,3 They target peptide bonds of proteins and/or peptides and some catalyze extensive protein-

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Section: Metzincin Family‐specific Featuresmentioning

confidence: 99%

Architecture and function of metallopeptidase catalytic domains

2013

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“…Metzincin exceptions lacking prosegments include the archaemetzincins, for which no hydrolytic activity has so far been reported, i.e. they might not need to be kept latent (41,42); the toxilysin EcxA from Escherichia coli, whose soluble expression requires co-expression with its cognate EcxB subunit, thus pointing to a chaperone-like function for this ancillary subunit (43)(44)(45); the cholerilysin StcE from E. coli, for which an N-terminal immunoglobulin-like domain may assist the downstream catalytic moiety in proper folding (46); and igalysins, where an all-␤-domain of similar topology to immunoglobulin-like domains is likewise found at the N terminus of the catalytic moiety (see Protein Data Bank (PDB) access codes 4DF9 and 3P1V and Ref. 5).…”

Section: X-x-h-x-x-(g/n)-x-x-(h/d)mentioning

confidence: 99%

A Novel Mechanism of Latency in Matrix Metalloproteinases

López-Pelegrín

Książek

Karim

et al. 2015

Journal of Biological Chemistry

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Background: Animal and plant matrix metalloproteinases (MMPs) are kept zymogenic through large prodomains and a cysteine-switch mechanism. Results: Bacterial MMP karilysin has only a short N-terminal peptide upstream of the catalytic domain, which lacks cysteines. Conclusion: This peptide inhibits through an aspartate-switch mechanism and also exerts other functions of authentic prodomains. Significance: Karilysin is kept latent by a novel mechanism for MMPs.

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“…B. anthracis , B. cereus, and B. thuringiensis each carry multiple apparent inhA genes with transcription of each gene subject to different regulation (223, 224). Autolytically processed active InhA1 of B. anthracis cleaves multiple host proteins and other proteins in the B. anthracis secretome (225, 226). A B. anthracis inhA1- null mutant is attenuated in a murine model for anthrax (227).…”

Section: Toxinsmentioning

confidence: 99%

The Bacillus cereus Group: Bacillus Species with Pathogenic Potential

2019

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The “Bacillus cereus group” includes several Bacillus species with closely related phylogeny. The most well-studied members of the group, Bacillus anthracis, B. cereus, and B. thuringiensis are known for their pathogenic potential. Here we present the historical rationale for speciation and discuss shared and unique features of these bacteria. Aspects of cell morphology and physiology, and genome sequence similarity and gene synteny support close evolutionary relationships for these three species. For many strains, distinct differences in virulence factor synthesis provide facile means for species assignment. B. anthracis is the causative agent of anthrax. Some B. cereus strains are commonly recognized as food poisoning agents, but strains can also cause localized wound and eye infections as well as systemic disease. Certain B. thuringiensis strains are entomopathogens and have been commercialized for use as biopesticides, while some strains have been reported to cause infection in immunocompromised individuals. In this chapter we compare and contrast B. anthracis, B. cereus, and B. thuringiensis, including ecology, cell structure and development, virulence attributes, gene regulation and genetic exchange systems, and experimental models of disease.

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A Different Look for AB5 Toxins

Cited by 8 publications

References 13 publications

Architecture and function of metallopeptidase catalytic domains

Architecture and function of metallopeptidase catalytic domains

A Novel Mechanism of Latency in Matrix Metalloproteinases

The Bacillus cereus Group: Bacillus Species with Pathogenic Potential

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