Use este identificador para citar ou linkar para este item: https://repositorio.ufpa.br/jspui/handle/2011/15635
Tipo: Artigo de Periódico
Data do documento: 2014
Autor(es): HASSAN, Syed Shah
TIWARI, Sandeep
GUIMARÃES, Luís Carlos
BACHA, Syed Babar Jamal
FOLADOR, Edson Luiz
SHARMA, Neha Barve
SOARES, Siomar de Castro
ALMEIDA, Sintia Silva de
ALI, Amjad
ISLAM, Arshad
PÓVOA, Fabiana Dias
ABREU, Vinicius Augusto Carvalho de
JAIN, Neha
FERREIRA, Rafaela Salgado
BHATTACHARYA, Antaripa
JUNEJA, Lucky
MIYOSHI, Anderson
SILVA, Artur Luiz da Costa da
BARH, Debmalya
TURJANSKI, Adrian Gustavo
AZEVEDO, Vasco Ariston de Carvalho
Afiliação do(s) Autor(es): SILVA, A. L. C. Universidade Federal do Pará
Título: Proteome scale comparative modeling for conserved drug and vaccine targets identification in Corynebacterium pseudotuberculosis
Citar como: HASSAN, Syed Shah et al. Proteome scale comparative modeling for conserved drug and vaccine targets identification in Corynebacterium pseudotuberculosis. BMC Genomics, online, v. 15, n. S3, p. 1-19, 2019. Supl. 7. DOI: https://doi.org/10.1186/1471-2164-15-S7-S3. Disponível em: http://repositorio.ufpa.br/jspui/handle/2011/15635. Acesso em:.
Abstract: Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to a broad spectrum of hosts, including ruminants, thereby threatening economic and dairy industries worldwide. Currently there is no effective drug or vaccine available against Cp. To identify new targets, we adopted a novel integrative strategy, which began with the prediction of the modelome (tridimensional protein structures for the proteome of an organism, generated through comparative modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan-modelomics approach identified a set of 331 conserved proteins having 95-100% intra-species sequence similarity. Next, we combined subtractive proteomics and modelomics to reveal a set of 10 Cp proteins, which may be essential for the bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied all criteria of being putative targets. Additionally, we subjected these 4 proteins to virtual screening of a drug-like compound library. In all cases, molecules predicted to form favorable interactions and which showed high complementarity to the target were found among the top ranking compounds. The remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have homologs in the host proteomes. Their active site cavities were compared to the respective cavities in host proteins. We propose that some of these proteins can be selectively targeted using structure-based drug design approaches (SBDD). Our results facilitate the selection of C. pseudotuberculosis putative proteins for developing broad-spectrum novel drugs and vaccines. A few of the targets identified here have been validated in other microorganisms, suggesting that our modelome strategy is effective and can also be applicable to other pathogens.
Palavras-chave: Corynebacterium pseudotuberculosis
Título do Periódico: BMC Genomics
ISSN: 1471-2164
País: Reino Unido
Instituição: BioMed Central Ltd
Tipo de Acesso: Acesso Aberto
Identificador DOI: 10.1186/1471-2164-15-S7-S3
Aparece nas coleções:Artigos Científicos - ICB

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