A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

Alves-Ferreira, Marcelo; Guimarães, Ana Carolina Ramos; Capriles, Priscila Vanessa da Silva Zabala; Dardenne, Laurent E.; Degrave, Wim

doi:10.1590/s0074-02762009000800006

Cited by 29 publications

(24 citation statements)

References 112 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This method would predict and infer the biological functions and genomic sequences. The enzymes present only in the bacterium and not the host were selected, and the corresponding protein sequences were retrieved [16].…”

Section: Metabolic Pathway Analysismentioning

confidence: 99%

“In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

Mahendran

Jeyabasker

Manoharan

et al. 2017

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objective: Syphilis is a sexually transmitted infection caused by the spirochaete, Treponema pallidum subspecies Pallidum nichols. In this study, a comparative metabolic pathway analysis and molecular docking were performed to identify putative drug targets. Methods:The biochemical pathways of T. pallidum subs. P. nichols and Homo sapiens were compared using kyoto encyclopedia of genes and genomes pathway(KEGG). The amino acid sequence of the selected enzymes were retrieved and Blastp was performed. Out of 9 enzymes, enolase was modeled using ModWeb, and the structure was validated using RAMPAGE. The active sites were identified using Metapocket 2.0 and further docked using AutoDock 4.2. Results:The enzymes which were not similar to that of H. sapiens were filtered out as potential drug targets. A total of 9 enzymes were retrieved which were present only in T. pallidum subs. P. nichols. The structure obtained from Homology modeling was validated using RAMPAGE which showed 96% of the residues in the favorable regions and 3% of the residues in the allowed region. Since the result obtained from RAMPAGE showed structural reliability further active sites were predicted. The docking analysis results showed the interaction between enolase and doxycycline. The atom H42 displayed in green has interacted with OD1 (Asp 317) with a distance of 1.9 Å depicts the best interaction and the structures were visualized using PyMol.Conclusion: Through this study, doxycycline which has antibacterial effect and a derivative of tetracycline could be one of the potential ligands against enolase.

show abstract

Section: Metabolic Pathway Analysismentioning

confidence: 99%

“In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

Mahendran

Jeyabasker

Manoharan

et al. 2017

Asian J Pharm Clin Res

View full text Add to dashboard Cite

show abstract

“…The TriTrypDB database gives information on individual genes or chromosomal spans in their genomic context, including syntenic alignments with other kinetoplastid organisms. The TriTrypDB database has allowed in silico metabolic pathway analysis using genome information (Alves-Ferreira et al 2009 ). An inventory of predicted metabolic components and integrated metabolic networks of TriTryp is collected in publicly available databases, and a comprehensive review of many of these databases is provided in detail by Myler (Myler 2008 (Doyle et al 2009 ).…”

Section: Computational Approaches That Aid Drug Target Prioritizationmentioning

confidence: 99%

Selection of Molecular Targets for Drug Development Against Trypanosomatids

Smirlis

Soares

2013

Subcellular Biochemistry

View full text Add to dashboard Cite

Trypanosomatid parasites are a group of flagellated protozoa that includes the genera Leishmania and Trypanosoma, which are the causative agents of diseases (leishmaniases, sleeping sickness and Chagas disease) that cause considerable morbidity and mortality, affecting more than 27 million people worldwide. Today no effective vaccines for the prevention of these diseases exist, whereas current chemotherapy is ineffective, mainly due to toxic side effects of current drugs and to the emergence of drug resistance and lack of cost effectiveness. For these reasons, rational drug design and the search of good candidate drug targets is of prime importance. The search for drug targets requires a multidisciplinary approach. To this end, the completion of the genome project of many trypanosomatid species gives a vast amount of new information that can be exploited for the identification of good drug candidates with a prediction of "druggability" and divergence from mammalian host proteins. In addition, an important aspect in the search for good drug targets is the "target identification" and evaluation in a biological pathway, as well as the essentiality of the gene in the mammalian stage of the parasite, which is provided by basic research and genetic and proteomic approaches. In this chapter we will discuss how these bioinformatic tools and experimental evaluations can be integrated for the selection of candidate drug targets, and give examples of metabolic and signaling pathways in the parasitic protozoa that can be exploited for rational drug design.

show abstract

“…23 They identified analogous and specific enzymes in T. cruzi by comparing the parasite metabolic pathways with the corresponding human metabolic pathways. By focussing on energetic pathways (glycolysis, pentose phosphate shunt, Krebs cycle, oxidative phosphorylation, β-oxidation, amino acid metabolism), lipid pathways and polyamine pathways, they identified several enzymes that are analogous to those of humans.…”

Section: Drug Target Discovery Using Genome Informationmentioning

confidence: 99%

“…By focussing on energetic pathways (glycolysis, pentose phosphate shunt, Krebs cycle, oxidative phosphorylation, β-oxidation, amino acid metabolism), lipid pathways and polyamine pathways, they identified several enzymes that are analogous to those of humans. 23 They suggested that many of these enzymes could be potential new drug targets. 23 In a similar study, Capriles and co-workers performed a comparative analysis with the T. cruzi genome and the human genome and used comparative modelling techniques to predict 3D protein structures.…”

Section: Drug Target Discovery Using Genome Informationmentioning

confidence: 99%

“…23 They suggested that many of these enzymes could be potential new drug targets. 23 In a similar study, Capriles and co-workers performed a comparative analysis with the T. cruzi genome and the human genome and used comparative modelling techniques to predict 3D protein structures. 24 They were able to identify 397 T.…”

Section: Drug Target Discovery Using Genome Informationmentioning

confidence: 99%

See 1 more Smart Citation

Delivering on Promises? The Impact of Kinetoplastid Genomics on Sleeping Sickness, Chagas Disease and Leishmaniasis

Steverding

Grisard

2012

Advances in Microbial Ecology

View full text Add to dashboard Cite

A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

Cited by 29 publications

References 112 publications

“In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

“In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

Selection of Molecular Targets for Drug Development Against Trypanosomatids

Delivering on Promises? The Impact of Kinetoplastid Genomics on Sleeping Sickness, Chagas Disease and Leishmaniasis

Contact Info

Product

Resources

About