The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003

Boeckmann, Brigitte; Bairoch, Amos Marc; Apweiler, Rolf; Blatter, Marie-Claude; Estreicher, Anne; Gasteiger, Elisabeth; Martin, Maria Jesus; Michoud, Karine; O′Donovan, Claire; Phan, Isabelle; Pilbout, Sandrine; Schneider, Michel

doi:10.1093/nar/gkg095

Cited by 3,220 publications

(2,306 citation statements)

References 31 publications

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“…In addition, the proportions of charged, polar, and aromatic residues (such as arginine, aspartate, aspargine, tryptophan, and tyrosine) and of unorganized secondary structure elements, are much lower in the epitopes-excluded area. Moreover, the epitopes-excluded area tends to include residues that are more evolutionary conserved, either near the active site (Boeckmann et al, 2003) or at other locations. Assuming that these characteristics are important for antibody binding, this comparison thus stresses the point that the protein surface is not homogeneously antigenic, but is rather composed of regions that vary considerably according to their antigenic potential.…”

Section: Discussionmentioning

confidence: 99%

Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

210

233

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Characterizing B-cell epitopes is a fundamental step for understanding the immunological basis of bio-recognition. To date, epitope analyses have either been based on limited structural data, or sequence data alone. In this study, our null hypothesis was that the surface of the antigen is homogeneously antigenic. To test this hypothesis, a large dataset of antibody-antigen complex structures, together with crystal structures of the native antigens, has been compiled. Computational methods were developed and applied to detect and extract physico-chemical, structural, and geometrical properties that may distinguish an epitope from the remaining antigen surface. Rigorous statistical inference was able to clearly reject the null hypothesis showing that epitopes are distinguished from the remaining antigen surface in properties such as amino acid preference, secondary structure composition, geometrical shape, and evolutionary conservation. Specifically, epitopes were found to be significantly enriched with tyrosine and tryptophan, and to show a general preference for charged and polar amino acids. Additionally, epitopes were found to show clear preference for residing on planar parts of the antigen that protrude from the surface, yet with a rugged surface shape at the atom level. The effects of complex formation on the structural properties of the antigen were also computationally characterized and it is shown that epitopes undergo compression upon antibody binding. This correlates with the finding that epitopes are enriched with unorganized secondary structure elements that render them flexible. Thus, this study extends the understanding of the underlying processes required for antibody binding, and reveals new aspects of the antibody-antigen interaction.

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Section: Discussionmentioning

confidence: 99%

Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

210

233

View full text Add to dashboard Cite

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“…Mycobacterium tuberculosis mycothiol reductase (Mtr) sequence was retrieved from UniProtKB/TrEMBL database (primary accession number A0A0T9X864) (Boeckmann et al, 2003). To identify homologous sequences with known 3D structure, a BLASTP (proteinprotein Basic Local Alignment Search Tool) search was carried out against the protein data bank (PDB) (Altschul et al, 1990;Bernstein et al, 1977).…”

Section: Homology Modellingmentioning

confidence: 99%

In vitro and In vivo antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of action

Lall

Kumar

Meyer

et al. 2016

Journal of Ethnopharmacology

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Ethnopharmacological relevance: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma. TB is prevalent in immune-compromised patients and it is evident that TB-drugs cause hepatotoxicity. The objective of the present study was therefore to evaluate the antimycobacterial activity of the 2 ethanolic extract of E. natalensis against TB and its hepatoprotective and immunomodulatory activities. Materials and methods:The antimycobacterial, antioxidant, hepatoprotective, immunomodulatory activity and cytotoxicity of the ethanolic extract of the shoots of E. natalensis were determined in vitro. The mechanism of action of the antituberculosis activity was determined by investigating the inhibitory effect on mycothiol disulfide reductase enzyme. Furthermore, the acute, sub-acute toxicity (50-2000 mg/kg) and antimycobacterial effect (300 mg/kg) of E. natalensis shoot extract were investigated in Balb/c mice.Hepatoprotective activity of the extract (50-150 mg/kg) was evaluated on isoniazid and rifampicin (50 mg/kg; i.p.) induced hepatic damage in a rat model. Results:The minimum inhibitory concentration of the extract was found to be 125 µg/ml against Mycobacterium tuberculosis. The extracts fifty percent inhibitory concentration (IC 50 ) against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical was found to be 22.55 µg/ml. The plant showed a hepatoprotective effect (50% at 12.5 µg/ml) and the ability to increase Thelper 1 cell cytokines; Interleukin 12, Interleukin 2 and Interferon α by up to 12 fold and the ability to decrease the T-helper 2 cell cytokine Interleukin 10 4 fold when compared to baseline cytokine production. No cellular toxicity was observed in primary peripheral blood mononuclear cells (PBMC's) and two secondary cell lines; U937 monocytes and Chang liver cells (a derivative of the HepG2 cell line). During mechanistic studies, the extract showed a 50% inhibition of mycothiol reductase activity at 38.62 µg/ml. During the acute and subacute studies, E. natalensis exhibited no toxic effect and the fifty percent lethal dose (LD 50 ) was established to be above 2000 mg/kg. The extract was able to reduce the mycobacterial load (1.5-fold reduction) in infected mice. Isoniazid and rifampicin caused significant hepatic damage in rats, and the extract was able to reduce the toxicity by 15% and 40% at 50 and 150 mg/kg respectively. Conclusion:The present study supports the traditional usage of the plant against tuberculosis symptoms. The study showed the ability of E. natalensis shoot extract to inhibit mycobacterial growth, stimulate an appropriate immune response and have a hepatic protective effect. Due to the ...

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“…This is particularly true for genomic data where high throughput is the priority. The best-annotated data are the painstakingly annotated protein data found in the SwissProt database [6]. This is accessible directly or through the main database sites (Box 1), but this is only a subset of all that is available.…”

Section: Homologymentioning

confidence: 99%