Exploring the interaction between Mycobacterium tuberculosis enolase and human plasminogen using computational methods and experimental techniques
| العنوان: | Exploring the interaction between Mycobacterium tuberculosis enolase and human plasminogen using computational methods and experimental techniques |
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| المؤلفون: | Amit Rahi, Andrew M. Lynn, Rakesh Bhatnagar, Damini Singh, Alisha Dhiman, Mohd Rehan |
| المصدر: | Journal of Cellular Biochemistry. 119:2408-2417 |
| بيانات النشر: | Wiley, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Gene isoform, 030106 microbiology, Lysine, Enolase, Biochemistry, Protein Structure, Secondary, Mycobacterium tuberculosis, 03 medical and health sciences, Bacterial Proteins, Humans, Protein Isoforms, Molecular Biology, Protein secondary structure, Alanine, Binding Sites, biology, Plasminogen, Cell Biology, biology.organism_classification, Triple mutant, Molecular Docking Simulation, 030104 developmental biology, Docking (molecular), Phosphopyruvate Hydratase, Mutation, Protein Binding |
| الوصف: | Surface localized microbial enolases' binding with human plasminogen has been increasingly proven to have an important role in initial infection cycle of several human pathogens.Likewise, surface localized Mycobacterium tuberculosis (Mtb) enolase also binds to human plasminogen, and this interaction may entail crucial consequences for granuloma stability. The current study is the first attempt to explore the plasminogen interacting residues of enolase from Mtb. Beginning with the structural modeling of Mtbenolase, the binding pose of Mtbenolase and human plasminogen was predicted using protein-protein docking simulations. The binding pose revealed the interface region with interacting residues and molecular interactions. Next, the interacting residues were refined and ranked by using various criteria. Finally, the selected interacting residues were tested experimentally for their involvement in plasminogen binding. The two consecutive lysine residues, Lys-193 and Lys-194, turned out to be active residues for plasminogen binding. These residues when substituted for alanine along with the most active residue Lys-429 i.e., the triple mutant (K193A + K194A + K429A) Mtb enolase, exhibited40% reduction in plasminogen binding. It is worth noting that Mtb enolase lost nearly half of the plasminogen binding activity with only three simultaneous substitutions, without any significant secondary structure perturbation. Further, the sequence comparison between Mtb and human enolase isoforms suggests the possibility of selective targeting of Mtb enolase to obstruct binding of human plasminogen. This article is protected by copyright. All rights reserved |
| تدمد: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.26403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ce821b257f2b3c663705591c356b35f https://doi.org/10.1002/jcb.26403 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9ce821b257f2b3c663705591c356b35f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974644 07302312 |
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| DOI: | 10.1002/jcb.26403 |