How to use the <scp><i>MEROPS</i></scp> database and website to help understand peptidase specificity

Rawlings, Neil D.; Bateman, Alex

doi:10.1002/pro.3948

Cited by 58 publications

(51 citation statements)

References 28 publications

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“…However, comparing selenok's self-cleavage with these examples is problematic. Selfcleavage is often enzymatic and carried out by proteolytic proteins (i.e., proteases) that catalyze peptide bond cleavage by either hydrolysis or elimination (as classified in (Rawlings & Bateman, 2021)). The enzymes that employ hydrolysis commonly use nucleophilic residues such as Cys, Glu, and Asp, but other residues and metals have also been found to contribute to those cleavage mechanisms (Klein et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Unconventional Self-Cleavage of Selenoprotein K

Cheng¹,

Liu

Mb³

et al. 2021

Preprint

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Through known association with other proteins, human selenoprotein K (selenok) is currently implicated in the palmitoylation of proteins, degradation of misfolded proteins, innate immune response, and the life cycle of SARS-CoV-2 virus. However, neither the catalytic function of selenok's selenocysteine (Sec), which, curiously, resides in an intrinsically disordered protein segment nor selenok's specific role in these pathways are known to date. This report casts these questions in a new light as it describes that selenok is able -both in vitro and in vivo- to cleave some of its own peptide bonds. The cleavages not only release selenok segments that contain its reactive Sec, but as the specific cleavage sites were identified, they proved to cluster tightly near sites through which selenok interacts with protein partners. Furthermore, it is shown that selenok's cleavage activity is neither restricted to itself nor promiscuous but selectively extends to at least one of its protein partners. Together, selenok's cleavage ability and its features have all hallmarks of a regulatory mechanism that could play a central role in selenok's associations with other proteins and its cellular functions overall.

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Section: Discussionmentioning

confidence: 99%

The Unconventional Self-Cleavage of Selenoprotein K

Cheng¹,

Liu

Mb³

et al. 2021

Preprint

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“…Predicted protein-coding genes were mapped on Cazy with DBCan ( Yin et al, 2012 ) modified like in Muszewska et al (2017a) , MEROPS protease evalue 1E-10 ( Rawlings and Bateman, 2020 ), PFAM evalue 0.001 ( El-Gebali et al, 2019 ), INTERPROScan 5.28-67 (v( Jones et al, 2014 )), CDD evalue 1E-5 ( Lu et al, 2020 ), AntiSMASH 4.0 (–transatpks_da– clusterblast–subclusterblast–knownclusterblast–smcogs–cassis–borderpredict–full-hmmer) ( Blin et al, 2017 ), TCDB evalue 1E-5 ( Saier et al, 2016 ). RNAi components were filtered with an evalue of 1E-10.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Potential, Ecology and Presence of Associated Bacteria Is Reflected in Genomic Diversity of Mucoromycotina

et al. 2021

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Mucoromycotina are often considered mainly in pathogenic context but their biology remains understudied. We describe the genomes of six Mucoromycotina fungi representing distant saprotrophic lineages within the subphylum (i.e., Umbelopsidales and Mucorales). We selected two Umbelopsis isolates from soil (i.e., U. isabellina, U. vinacea), two soil-derived Mucor isolates (i.e., M. circinatus, M. plumbeus), and two Mucorales representatives with extended proteolytic activity (i.e., Thamnidium elegans and Mucor saturninus). We complement computational genome annotation with experimental characteristics of their digestive capabilities, cell wall carbohydrate composition, and extensive total lipid profiles. These traits inferred from genome composition, e.g., in terms of identified encoded enzymes, are in accordance with experimental results. Finally, we link the presence of associated bacteria with observed characteristics. Thamnidium elegans genome harbors an additional, complete genome of an associated bacterium classified to Paenibacillus sp. This fungus displays multiple altered traits compared to the remaining isolates, regardless of their evolutionary distance. For instance, it has expanded carbon assimilation capabilities, e.g., efficiently degrades carboxylic acids, and has a higher diacylglycerol:triacylglycerol ratio and skewed phospholipid composition which suggests a more rigid cellular membrane. The bacterium can complement the host enzymatic capabilities, alter the fungal metabolism, cell membrane composition but does not change the composition of the cell wall of the fungus. Comparison of early-diverging Umbelopsidales with evolutionary younger Mucorales points at several subtle differences particularly in their carbon source preferences and encoded carbohydrate repertoire. Nevertheless, all tested Mucoromycotina share features including the ability to produce 18:3 gamma-linoleic acid, use TAG as the storage lipid and have fucose as a cell wall component.

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“…Predicted protein-coding genes were mapped on Cazy with DBCan [140] modified like in [141], MEROPS protease evalue 1E-10 [142], PFAM evalue 0.001 [143], INTERPROScan 5.28-67 (v[144]), CDD evalue 1E-5 [145], AntiSMASH 4.0 (--transatpks_da --clusterblast --subclusterblast --knownclusterblast --smcogs --cassis --borderpredict --full-hmmer) [146], TCDB evalue 1E-5 [147]. RNAi components were filtered with an evalue of 1E-10.…”

Section: Methodsmentioning

confidence: 99%

Metabolic potential, ecology and presence of endohyphal bacteria is reflected in genomic diversity of Mucoromycotina

Muszewska

Okrasińska

Steczkiewicz

et al. 2020

Preprint

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We describe the genomes of six Mucoromycotina fungi representing distant saprotrophic lineages within the subphylum (i.e. Umbelopsidales and Mucorales). We selected two Umbelopsis isolates from soil (i.e. U. isabellina, U. vinacea), two soil-derived Mucor isolates (i.e. M. circinatus, M. plumbeus), and two Mucorales representatives with extended proteolytic activity (i.e. Thamnidium elegans and Mucor saturninus). We complement genome analyses with a description of their digestive capabilities, their cell wall carbohydrate composition, and total lipid profiles. Finally, we link the presence of endohyphal bacteria with observed characteristics.One of the genomes, Thamnidium elegans, harbours a complete genome of an associated bacterium classified to Paenibacillus sp. This fungus displays multiple altered traits compared to remaining isolates regardless of their evolutionary distance. T. elegans has expanded carbon assimilation capabilities particularly efficiently degrades carboxylic acids, has a higher diacylglycerol: triacylglycerol ratio and phospholipid composition suggesting a more rigid cellular membrane. Comparison of early-diverging Umbelopsidales with evolutionary younger Mucorales points at several differences particularly in their carbon source preferences and encoded carbohydrate repertoire. All tested Mucoromycotina shares features including the ability to produce 18:3 gamma-linoleic acid and fucose as a cell wall component.Author SummaryIn our paper, we report on the genomic sequences of six Mucoromycotina strains and an associated bacterium from Paenibacillus genus. Mucoromycotina are often studied in pathogenic context albeit their basic biology remains understudied. This manuscript expands on the collection of currently sequenced Mucorales and Umbelopsidales, including the first sequenced Thamnidium isolate, which was sequenced together with a Paenibacillus bacterium. The interaction with a bacterial partner alters the metabolism, cell membrane composition but not the exoskeleton of the fungus. The associated bacterium provided multiple enzymes that significantly expanded the digestive capabilities of the fungal host. Parallel sequencing and phenotyping of Mucorales and Umbelopsidales enabled us to look at the differences of both lineages within Mucoromycotina. We demonstrate that the predicted digestive capabilities are in line with experimental validation. Based on the cell wall composition data and genomic underpinnings of carbohydrate metabolism we were able to confirm the universal presence of fucose in Mucoromycotina cell walls. Fatty acid, phospholipid and acylglycerol composition support the usage of 18:3 gamma-linoleic acid as a chemotaxonomic marker of Mucoromycotina and corroborate TAG as a dominant storage lipid in these organisms.Genomic features, digestive capabilities, fatty acid composition differ between Mucorales and Ubelopsidales pointing at subtle but significant changes in the course of Mucoromycotina radiation.

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How to use the MEROPS database and website to help understand peptidase specificity

Cited by 58 publications

References 28 publications

The Unconventional Self-Cleavage of Selenoprotein K

The Unconventional Self-Cleavage of Selenoprotein K

Metabolic Potential, Ecology and Presence of Associated Bacteria Is Reflected in Genomic Diversity of Mucoromycotina

Metabolic potential, ecology and presence of endohyphal bacteria is reflected in genomic diversity of Mucoromycotina

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