The MEROPS Database as a Protease Information System

Barrett, Alan J.; Rawlings, Neil D.; O'Brien, Emmet A.

doi:10.1006/jsbi.2000.4332

Cited by 130 publications

(106 citation statements)

References 12 publications

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“…Some common examples include pepsin, cathepsin D, chymosin, and the microbial penicillopepsin, with pepsin being the most studied AP. These enzymes may be intracellular or extracellular, and they are active under acidic conditions (pH 2 to 5) and have molecular masses ranging from 35 kDa to 50 kDa and isoelectric points (pIs) of 3.9 to 4.9 (3,12,42). The APs have two reactive aspartic acid residues in their catalytic sites that are essential for their functioning.…”

mentioning

confidence: 99%

Identification and Partial Characterization of Extracellular Aspartic Protease Genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384

Reid

Theron

Toit

et al. 2012

Appl Environ Microbiol

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ABSTRACTThe extracellular acid proteases of non-Saccharomyceswine yeasts may fulfill a number of roles in winemaking, which include increasing the available nitrogen sources for the growth of fermentative microbes, affecting the aroma profile of the wine, and potentially reducing protein haze formation. These proteases, however, remain poorly characterized, especially at genetic level. In this study, two extracellular aspartic protease-encoding genes were identified and sequenced, from two yeast species of enological origin: one gene fromMetschnikowia pulcherrimaIWBT Y1123, namedMpAPr1, and the other gene fromCandida apicolaIWBT Y1384, namedCaAPr1.In silicoanalysis of these two genes revealed a number of features peculiar to aspartic protease genes, and both the MpAPr1 and CaAPr1 putative proteins showed homology to proteases of yeast genera. Heterologous expression ofMpAPr1inSaccharomyces cerevisiaeYHUM272 confirmed that it encodes an aspartic protease. MpAPr1 production, which was shown to be constitutive, and secretion were confirmed in the presence of bovine serum albumin (BSA), casein, and grape juice proteins. TheMpAPr1gene was found to be present in 12 otherM. pulcherrimastrains; however, plate assays revealed that the intensity of protease activity was strain dependent and unrelated to the gene sequence.

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confidence: 99%

Identification and Partial Characterization of Extracellular Aspartic Protease Genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384

Reid

Theron

Toit

et al. 2012

Appl Environ Microbiol

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“…Amino acid side chains of substrates occupy proteolytic enzyme sub-sites in the groove, designated as S3, S2, S1, S1', S2', S3', that bind to corresponding substrate/inhibitor residues P3, P2, P1, P1', P2', P3' with respect to the cleavable peptide bond (Figure 4). After the proteinaceous substrate cleavage, at least two smaller peptides can be generated (Figure 4) [12][13][14][15] . Proteases are subdivided into two major groups depending on their site of action: exopeptidases and endopeptidases.…”

Section: Proteolytic Enzymes and Their Inhibitors: An Overviewmentioning

confidence: 99%

“…Similarly, endopeptidases are classified according to essential catalytic residues at their active sites in: serine, metallo, glutamic, threonine, cysteine and aspartic endopeptidases ( Figure 5). Conversely, there are a few miscellaneous proteases that do not precisely fit into the standard classification [12][13][14][15] . The class of a protease is characteristically determined according to the effects of proteolytic inhibitors on the enzymatic activity [16,17] .…”

Section: Proteolytic Enzymes and Their Inhibitors: An Overviewmentioning

confidence: 99%

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

Santos¹

2011

WJBC

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The treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells, which are similar in several biochemical and genetic aspects to host cells. Aggravating this scenario, very few antifungal and anti-trypanosomatidal agents are in clinical use and, therefore, therapy is limited by drug safety considerations and their narrow spectrum of activity, efficacy and resistance. The search for new bioactive agents against fungi and trypanosomatids has been expanded because progress in biochemistry and molecular biology has led to a better understanding of important and essential pathways in these microorganisms including nutrition, growth, proliferation, signaling, differentiation and death. In this context, proteolytic enzymes produced by these eukaryotic microorganisms are appointed and, in some cases, proven to be excellent targets for searching novel natural and/or synthetic pharmacological compounds, in order to cure or prevent invasive fungal/trypanosomatid diseases. With this task in mind, our research group and others have focused on aspartic-type proteases, since the activity of this class of hydrolytic enzymes is directly implicated in several facets of basic biological processes of both fungal and trypanosomatid cells as well as due to the participation in numerous events of interaction between these microorganisms and host structures. In the present paper, a concise revision of the beneficial effects of aspartic protease inhibitors, with emphasis on the aspartic protease inhibitors used in the anti-human immunodeficiency virus therapy, will be presented and discussed using our experience with the following microbial models: the yeast Candida albicans , the filamentous fungus Fonsecaea pedrosoi and the protozoan trypanosomatid Leishmania amazonensis .

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“…The Cysteine proteases, including papains, cathepsins, calpains, caspases and lugumain, represent a biologically important clan of protein, which are important therapeutic target of tumor, inflammation and auto-immune disease [12][13][14] . So it is no surprise that Michael acceptors have the potential of anti-tumor activity.…”

Section: Introductionmentioning

confidence: 99%

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

Deng

Kong

Zhao

et al. 2012

Nat. Prod. Bioprospect.

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Abstract:A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated. Starting from fifteen structurally diverse natural products, a focused library featured by Michael acceptors is constructed with IBX mediated oxidation. Biological assay on five tumor cell lines indicates that four Michael acceptors, 8a, 11a, 12a, 14a, are with improved cytotoxicity (3-10 folds more potent than the parent compounds), which merit further investigations. Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor. The results suggest that the strategy is not only effective and relatively high discovery rate (28%), but also resource saving.

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The MEROPS Database as a Protease Information System

Cited by 130 publications

References 12 publications

Identification and Partial Characterization of Extracellular Aspartic Protease Genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384

Identification and Partial Characterization of Extracellular Aspartic Protease Genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

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