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Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization

Protein prenylation is a post-translational modification controlling the localization, activity, and protein–protein interactions of small GTPases, including the Ras superfamily. This covalent attachment of either a farnesyl (15 carbon) or a geranylgeranyl (20 carbon) isoprenoid group is catalyzed b...

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Autores principales: Marchwicka, Aleksandra, Kamińska, Daria, Monirialamdari, Mohsen, Błażewska, Katarzyna M., Gendaszewska-Darmach, Edyta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141697/
https://www.ncbi.nlm.nih.gov/pubmed/35628237
http://dx.doi.org/10.3390/ijms23105424
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author Marchwicka, Aleksandra
Kamińska, Daria
Monirialamdari, Mohsen
Błażewska, Katarzyna M.
Gendaszewska-Darmach, Edyta
author_facet Marchwicka, Aleksandra
Kamińska, Daria
Monirialamdari, Mohsen
Błażewska, Katarzyna M.
Gendaszewska-Darmach, Edyta
author_sort Marchwicka, Aleksandra
collection PubMed
description Protein prenylation is a post-translational modification controlling the localization, activity, and protein–protein interactions of small GTPases, including the Ras superfamily. This covalent attachment of either a farnesyl (15 carbon) or a geranylgeranyl (20 carbon) isoprenoid group is catalyzed by four prenyltransferases, namely farnesyltransferase (FTase), geranylgeranyltransferase type I (GGTase-I), Rab geranylgeranyltransferase (GGTase-II), and recently discovered geranylgeranyltransferase type III (GGTase-III). Blocking small GTPase activity, namely inhibiting prenyltransferases, has been proposed as a potential disease treatment method. Inhibitors of prenyltransferase have resulted in substantial therapeutic benefits in various diseases, such as cancer, neurological disorders, and viral and parasitic infections. In this review, we overview the structure of FTase, GGTase-I, GGTase-II, and GGTase-III and summarize the current status of research on their inhibitors.
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spelling pubmed-91416972022-05-28 Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization Marchwicka, Aleksandra Kamińska, Daria Monirialamdari, Mohsen Błażewska, Katarzyna M. Gendaszewska-Darmach, Edyta Int J Mol Sci Review Protein prenylation is a post-translational modification controlling the localization, activity, and protein–protein interactions of small GTPases, including the Ras superfamily. This covalent attachment of either a farnesyl (15 carbon) or a geranylgeranyl (20 carbon) isoprenoid group is catalyzed by four prenyltransferases, namely farnesyltransferase (FTase), geranylgeranyltransferase type I (GGTase-I), Rab geranylgeranyltransferase (GGTase-II), and recently discovered geranylgeranyltransferase type III (GGTase-III). Blocking small GTPase activity, namely inhibiting prenyltransferases, has been proposed as a potential disease treatment method. Inhibitors of prenyltransferase have resulted in substantial therapeutic benefits in various diseases, such as cancer, neurological disorders, and viral and parasitic infections. In this review, we overview the structure of FTase, GGTase-I, GGTase-II, and GGTase-III and summarize the current status of research on their inhibitors. MDPI 2022-05-12 /pmc/articles/PMC9141697/ /pubmed/35628237 http://dx.doi.org/10.3390/ijms23105424 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Marchwicka, Aleksandra
Kamińska, Daria
Monirialamdari, Mohsen
Błażewska, Katarzyna M.
Gendaszewska-Darmach, Edyta
Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title_full Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title_fullStr Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title_full_unstemmed Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title_short Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization
title_sort protein prenyltransferases and their inhibitors: structural and functional characterization
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141697/
https://www.ncbi.nlm.nih.gov/pubmed/35628237
http://dx.doi.org/10.3390/ijms23105424
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