Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions.
Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world. These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions, such as redox homeo...
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ftdoajarticles:oai:doaj.org/article:c5022e7318554ff1bb578a86e9ed4bd0 2023-05-15T15:02:40+02:00 Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. Leah M Wachsmuth Meredith G Johnson Jason Gavenonis 2017-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005720 https://doaj.org/article/c5022e7318554ff1bb578a86e9ed4bd0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5507555?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005720 https://doaj.org/article/c5022e7318554ff1bb578a86e9ed4bd0 PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005720 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005720 2022-12-31T13:27:16Z Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world. These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions, such as redox homeostasis and nucleotide synthesis. Computational alanine scanning of these protein-protein interfaces has revealed a host of potentially ligandable sites on several established and emerging anti-parasitic drug targets. Analysis of interfaces with multiple clustered hotspots has suggested several potentially inhibitable protein-protein interactions that may have been overlooked by previous large-scale analyses focusing solely on secondary structure. These protein-protein interactions provide a promising lead for the development of new peptide and macrocycle inhibitors of these enzymes. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 6 e0005720 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Leah M Wachsmuth Meredith G Johnson Jason Gavenonis Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world. These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions, such as redox homeostasis and nucleotide synthesis. Computational alanine scanning of these protein-protein interfaces has revealed a host of potentially ligandable sites on several established and emerging anti-parasitic drug targets. Analysis of interfaces with multiple clustered hotspots has suggested several potentially inhibitable protein-protein interactions that may have been overlooked by previous large-scale analyses focusing solely on secondary structure. These protein-protein interactions provide a promising lead for the development of new peptide and macrocycle inhibitors of these enzymes. |
format |
Article in Journal/Newspaper |
author |
Leah M Wachsmuth Meredith G Johnson Jason Gavenonis |
author_facet |
Leah M Wachsmuth Meredith G Johnson Jason Gavenonis |
author_sort |
Leah M Wachsmuth |
title |
Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
title_short |
Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
title_full |
Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
title_fullStr |
Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
title_full_unstemmed |
Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions. |
title_sort |
essential multimeric enzymes in kinetoplastid parasites: a host of potentially druggable protein-protein interactions. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005720 https://doaj.org/article/c5022e7318554ff1bb578a86e9ed4bd0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005720 (2017) |
op_relation |
http://europepmc.org/articles/PMC5507555?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005720 https://doaj.org/article/c5022e7318554ff1bb578a86e9ed4bd0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005720 |
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PLOS Neglected Tropical Diseases |
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11 |
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6 |
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e0005720 |
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1766334593695219712 |