Matrix metalloproteinases outside vertebrates

Marino-Puertas, Laura; Goulas, Theodoros; Gomis‐Rüth, F. Xavier

doi:10.1016/j.bbamcr.2017.04.003

Cited by 28 publications

(24 citation statements)

References 144 publications

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“…Zymogenicity in MPs was first structurally analysed in the 1990s for the funnelin metallocarboxypeptidases (Coll et al, 1991;Gomis-Rü th et al, 1995;Gomis-Rü th, 2008) and for mammalian MMPs (Becker et al, 1995;Morgunova et al, 1999;Tallant, Marrero et al, 2010). MMPs are found, often in several copies, in animals, plants, fungi, archaea, bacteria and viruses (Marino-Puertas et al, 2017), with 23 paralogs in humans. Mammalian MMP zymogens are inhibited by 70-90residue PSs upstream of the CD through a cysteine within a conserved motif, PRCGXPD.…”

Section: Promirolysin Latency In the Context Of Other Mpsmentioning

confidence: 99%

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

Guevara

Rodríguez-Banqueri

Książek

et al. 2020

IUCrJ

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Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54–Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segment traverses the active-site cleft in the opposite direction to the substrate, which precludes its cleavage. It is anchored to the mature enzyme through residue Arg21, which intrudes into the specificity pocket in cleft sub-site S1′. Moreover, residue Cys23 within a conserved cysteine–glycine motif blocks the catalytic zinc ion by a cysteine-switch mechanism, first described for mammalian matrix metallopeptidases. In addition, a 1.5 Å structure was obtained for a complex of mature mirolysin and a tetradecapeptide, which filled the cleft from sub-site S1′ to S6′. A citrate molecule in S1 completed a product-complex mimic that unveiled the mechanism of substrate binding and cleavage by mirolysin, the catalytic domain of which was already preformed in the zymogen. These results, including a preference for cleavage before basic residues, are likely to be valid for other unicellular pappalysins derived from archaea, bacteria, cyanobacteria, algae and fungi, including archetypal ulilysin from Methanosarcina acetivorans. They may further apply, at least in part, to the multi-domain orthologues of higher organisms.

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Section: Promirolysin Latency In the Context Of Other Mpsmentioning

confidence: 99%

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

Guevara

Rodríguez-Banqueri

Książek

et al. 2020

IUCrJ

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Section: Scheme 4 -Structures Of Prototypic Mp Zymogens (Ii) (A) Entmentioning

confidence: 99%

“…Although the cysteine-switch mechanism was derived from mammalian MMPs, sequence analyses revealed that plant MMPs likely also contain a pro-segment with a cysteine-switch motif, which, however, may occasionally diverge from the consensus 98,99 . Accordingly, this mechanism of latency seems to be widely conserved across eukaryotic MMPs 99 . Furthermore, the more distantly related members of the gametolysin family of MPs from green algae, such as unicellular Chlamydomonas reinhardtii and multicellular Volvox carteri, may likewise operate through a cysteine switch [99][100][101][102] .…”

Section: Scheme 4 -Structures Of Prototypic Mp Zymogens (Ii) (A) Entmentioning

confidence: 99%

Multiple Architectures and Mechanisms of Latency in Metallopeptidase Zymogens

et al. 2018

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Metallopeptidases cleave polypeptides bound in the active-site cleft of catalytic domains through a general base/acid mechanism. This involves a solvent molecule bound to a catalytic zinc and general regulation of the mechanism through zymogen-based latency. Sixty reported structures from 11 metallopeptidase families reveal that prosegments, mostly N-terminal of the catalytic domain, block the cleft regardless of their size. Prosegments may be peptides (5-14 residues), which are only structured within the zymogens, or large moieties (<227 residues) of one or two folded domains. While some prosegments globally shield the catalytic domain through a few contacts, others specifically run across the cleft in the same or opposite direction as a substrate, making numerous interactions. Some prosegments block the zinc by replacing the solvent with particular side chains, while others use terminal α-amino or carboxylate groups. Overall, metallopeptidase zymogens employ disparate mechanisms that diverge even within families, which supports that latency is less conserved than catalysis.

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“…However, orthologs of MMPs have been reported to occur rarely in fungi, strictly phylum Ascomycota and no activity data are available (Cerdà-Costa and Gomis-Rüth, 2014;Marino-Puertas et al, 2017). M-peptidases have also been implicated as virulence factors in various organisms (Gravi et al, 2012).…”

Section: Metallopeptidases and Cysteine Proteases Are The Most Abundamentioning

confidence: 99%

In silico Proteomic Analysis Provides Insights Into Phylogenomics and Plant Biomass Deconstruction Potentials of the Tremelalles

Aliyu

Gorte

Zhou

et al. 2020

Front. Bioeng. Biotechnol.

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Basidiomycetes populate a wide range of ecological niches but unlike ascomycetes, their capabilities to decay plant polymers and their potential for biotechnological approaches receive less attention. Particularly, identification and isolation of CAZymes is of biotechnological relevance and has the potential to improve the cache of currently available commercial enzyme cocktails toward enhanced plant biomass utilization. The order Tremellales comprises phylogenetically diverse fungi living as human pathogens, mycoparasites, saprophytes or associated with insects. Here, we have employed comparative genomics approaches to highlight the phylogenomic relationships among thirty-five Tremellales and to identify putative enzymes of biotechnological interest encoded on their genomes. Evaluation of the predicted proteomes of the thirty-five Tremellales revealed 6,918 putative carbohydrate-active enzymes (CAZYmes) and 7,066 peptidases. Two soil isolates, Saitozyma podzolica DSM 27192 and Cryptococcus sp. JCM 24511, show higher numbers harboring an average of 317 compared to a range of 267-121 CAZYmes for the rest of the strains. Similarly, the proteomes of the two soil isolates along with two plant associated strains contain higher number of peptidases sharing an average of 234 peptidases compared to a range of 226-167 for the rest of the strains. Despite these huge differences and the apparent enrichment of these enzymes among the soil isolates, the data revealed a diversity of the various enzyme families that does not reflect specific habitat type. Growth experiment on various carbohydrates to validate the predictions provides support for this view. Overall, the data indicates that the Tremellales could serve as a rich source of both CAZYmes and peptidases with wide range of potential biotechnological relevance.

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Matrix metalloproteinases outside vertebrates

Cited by 28 publications

References 144 publications

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

Multiple Architectures and Mechanisms of Latency in Metallopeptidase Zymogens

In silico Proteomic Analysis Provides Insights Into Phylogenomics and Plant Biomass Deconstruction Potentials of the Tremelalles

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