Cargando…

BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections

The search for new therapeutic targets and their implications in drug development remains an emerging scientific topic. BRCT-bearing proteins are found in Archaea, Bacteria, Eukarya, and viruses. They are traditionally involved in DNA repair, recombination, and cell cycle control. To carry out these...

Descripción completa

Detalles Bibliográficos
Autores principales: Peña-Guerrero, José, Fernández-Rubio, Celia, García-Sosa, Alfonso T., Nguewa, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386641/
https://www.ncbi.nlm.nih.gov/pubmed/37514027
http://dx.doi.org/10.3390/pharmaceutics15071839
_version_ 1785081717881569280
author Peña-Guerrero, José
Fernández-Rubio, Celia
García-Sosa, Alfonso T.
Nguewa, Paul A.
author_facet Peña-Guerrero, José
Fernández-Rubio, Celia
García-Sosa, Alfonso T.
Nguewa, Paul A.
author_sort Peña-Guerrero, José
collection PubMed
description The search for new therapeutic targets and their implications in drug development remains an emerging scientific topic. BRCT-bearing proteins are found in Archaea, Bacteria, Eukarya, and viruses. They are traditionally involved in DNA repair, recombination, and cell cycle control. To carry out these functions, BRCT domains are able to interact with DNA and proteins. Moreover, such domains are also implicated in several pathogenic processes and malignancies including breast, ovarian, and lung cancer. Although these domains exhibit moderately conserved folding, their sequences show very low conservation. Interestingly, sequence variations among species are considered positive traits in the search for suitable therapeutic targets, since non-specific drug interactions might be reduced. These main characteristics of BRCT, as well as its critical implications in key biological processes in the cell, have prompted the study of these domains as therapeutic targets. This review explores the possible roles of BRCT domains as therapeutic targets for drug discovery. We describe their common structural features and relevant interactions and pathways, as well as their implications in pathologic processes. Drugs commonly used to target these domains are also presented. Finally, based on their structures, we describe new drug design possibilities using modern and innovative techniques.
format Online
Article
Text
id pubmed-10386641
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103866412023-07-30 BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections Peña-Guerrero, José Fernández-Rubio, Celia García-Sosa, Alfonso T. Nguewa, Paul A. Pharmaceutics Review The search for new therapeutic targets and their implications in drug development remains an emerging scientific topic. BRCT-bearing proteins are found in Archaea, Bacteria, Eukarya, and viruses. They are traditionally involved in DNA repair, recombination, and cell cycle control. To carry out these functions, BRCT domains are able to interact with DNA and proteins. Moreover, such domains are also implicated in several pathogenic processes and malignancies including breast, ovarian, and lung cancer. Although these domains exhibit moderately conserved folding, their sequences show very low conservation. Interestingly, sequence variations among species are considered positive traits in the search for suitable therapeutic targets, since non-specific drug interactions might be reduced. These main characteristics of BRCT, as well as its critical implications in key biological processes in the cell, have prompted the study of these domains as therapeutic targets. This review explores the possible roles of BRCT domains as therapeutic targets for drug discovery. We describe their common structural features and relevant interactions and pathways, as well as their implications in pathologic processes. Drugs commonly used to target these domains are also presented. Finally, based on their structures, we describe new drug design possibilities using modern and innovative techniques. MDPI 2023-06-27 /pmc/articles/PMC10386641/ /pubmed/37514027 http://dx.doi.org/10.3390/pharmaceutics15071839 Text en © 2023 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
Peña-Guerrero, José
Fernández-Rubio, Celia
García-Sosa, Alfonso T.
Nguewa, Paul A.
BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title_full BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title_fullStr BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title_full_unstemmed BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title_short BRCT Domains: Structure, Functions, and Implications in Disease—New Therapeutic Targets for Innovative Drug Discovery against Infections
title_sort brct domains: structure, functions, and implications in disease—new therapeutic targets for innovative drug discovery against infections
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386641/
https://www.ncbi.nlm.nih.gov/pubmed/37514027
http://dx.doi.org/10.3390/pharmaceutics15071839
work_keys_str_mv AT penaguerrerojose brctdomainsstructurefunctionsandimplicationsindiseasenewtherapeutictargetsforinnovativedrugdiscoveryagainstinfections
AT fernandezrubiocelia brctdomainsstructurefunctionsandimplicationsindiseasenewtherapeutictargetsforinnovativedrugdiscoveryagainstinfections
AT garciasosaalfonsot brctdomainsstructurefunctionsandimplicationsindiseasenewtherapeutictargetsforinnovativedrugdiscoveryagainstinfections
AT nguewapaula brctdomainsstructurefunctionsandimplicationsindiseasenewtherapeutictargetsforinnovativedrugdiscoveryagainstinfections