Biopolym. Cell. 2019; 35(6): 448-466.
Bioinformatics
Identification and characterization of potential membrane-bound molecular drug targets of methicillin-resistant Staphylococcus aureus using in silico approaches
1Pernatii A. Yu., 1Volynets G. P., 1Protopopov M. V., 1, 2Prykhod’ko A. O., 1Sapelkin V. M., 1Pletnova L. V., 1, 2Matiushok V. I., 1Bdzhola V. G., 1Yarmoluk S. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
  2. LLC “Scientific and service firm “Otava”
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. The objective of this study was to identify the novel putative drug targets of methicil-lin-resistant S. aureus (MRSA) through subtractive proteome analysis. Methods. Identification of non-homologous proteins to the human proteome, search of MRSA essential genes and evaluation of drug target novelty were performed using protein BLAST server. Unique metabolic pathways identification was carried out using data and tools from KEGG (Kyoto Encyclopedia of Genes and Genomes). Prediction of sub-cellular proteins localization was performed using combination of tools PSORT v. 3.0.2, CELLO v. 2.5, iLoc-Gpos, and Pred-Lipo. Homology modeling was performed by web-servers SWISS-MODEL, Phyre2, I-TASSER, and program MODELLER. Results. Proteomes of six annotated methicillin-resistant strains, i.e., MRSA ATCC BAA-1680, H-EMRSA-15, LA MRSA ST398, MRSA 252, MRSA ST772, UTSW MRSA 55, have been taken to form the initial set. The proteome analysis of the MRSA strains in several consequent steps resulted in [the] identification of two molecular targets – diadenylate cyclase and D-alanyl-lipoteichoic acid biosynthesis (DltB) protein which meet the requirements of being essential, membrane-bound, non-homologous to human proteome, involved in unique metabolic pathways and new in terms of not having approved drugs. Using [the] homology modeling approach we have built three-dimensional structures of these proteins and predicted their ligand-binding sites. Conclusions. In this study using classical bioinformatics approaches we identified two molecular targets of MRSA – diadenylate cyclase and D-alanyl-lipoteichoic acid biosynthesis protein which can be used for further rational drug design in order to find novel therapeutic agents for the treatment of multidrug resistant staphylococcal infection.
Keywords: molecular drug targets, methicillin-resistant Staphylococcus aureus, MRSA, subtractive proteome analysis, homology modeling

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