Unmasking allosteric-binding sites: novel targets for GPCR drug discovery

Introduction: Unexpected non-apparent and hidden allosteric-binding sites are non-classical and non-apparent allosteric centers in 3-D X-ray protein structures until orthosteric or allosteric ligands bind to them. The orthosteric center of one protomer that modulates binding centers of the other pro...

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Detalles Bibliográficos
Autores: Casadó Anguera, Verònica, Casadó, Vicent
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/225750
Acceso en línea:https://hdl.handle.net/2445/225750
Access Level:acceso abierto
Palabra clave:Centres actius (Bioquímica)
Enzims al·lostèrics
Proteïnes G
Binding sites (Biochemistry)
Allosteric enzymes
G Proteins
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spelling Unmasking allosteric-binding sites: novel targets for GPCR drug discoveryCasadó Anguera, VerònicaCasadó, VicentCentres actius (Bioquímica)Enzims al·lostèricsProteïnes GBinding sites (Biochemistry)Allosteric enzymesG ProteinsIntroduction: Unexpected non-apparent and hidden allosteric-binding sites are non-classical and non-apparent allosteric centers in 3-D X-ray protein structures until orthosteric or allosteric ligands bind to them. The orthosteric center of one protomer that modulates binding centers of the other protomers within an oligomer is also an unexpected allosteric site. Furthermore, another partner protein can also produce these effects, acting as an unexpected allosteric modulator. Areas covered: This review summarizes both classical and non-classical allosterism. The authors focus on G protein-coupled receptor (GPCR) oligomers as a paradigm of allosteric molecules. Moreover, they show several examples of unexpected allosteric sites such as hidden allosteric sites in a protomer that appear after the interaction with other molecules and the allosterism exerted between orthosteric sites within GPCR oligomer, emphasizing on the allosteric modulations that can occur between binding sites. Expert opinion: The study of these new non-classical allosteric sites will expand the diversity of allosteric control on the function of orthosteric sites within proteins, whether GPCRs or other receptors, enzymes, or transporters. Moreover, the design of new drugs targeting these hidden allosteric sites or already known orthosteric sites acting as allosteric sites in protein homo- or hetero-oligomers will increase the therapeutic potential of allosterism.Informa Healthcare2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/225750Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1080/17460441.2022.2085684Expert Opinion on Drug Discovery, 2022, vol. 17, num.8, p. 897-923https://doi.org/10.1080/17460441.2022.2085684(c) Informa Healthcare, 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2257502026-05-27T06:46:51Z
dc.title.none.fl_str_mv Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
title Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
spellingShingle Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
Casadó Anguera, Verònica
Centres actius (Bioquímica)
Enzims al·lostèrics
Proteïnes G
Binding sites (Biochemistry)
Allosteric enzymes
G Proteins
title_short Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
title_full Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
title_fullStr Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
title_full_unstemmed Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
title_sort Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
dc.creator.none.fl_str_mv Casadó Anguera, Verònica
Casadó, Vicent
author Casadó Anguera, Verònica
author_facet Casadó Anguera, Verònica
Casadó, Vicent
author_role author
author2 Casadó, Vicent
author2_role author
dc.subject.none.fl_str_mv Centres actius (Bioquímica)
Enzims al·lostèrics
Proteïnes G
Binding sites (Biochemistry)
Allosteric enzymes
G Proteins
topic Centres actius (Bioquímica)
Enzims al·lostèrics
Proteïnes G
Binding sites (Biochemistry)
Allosteric enzymes
G Proteins
description Introduction: Unexpected non-apparent and hidden allosteric-binding sites are non-classical and non-apparent allosteric centers in 3-D X-ray protein structures until orthosteric or allosteric ligands bind to them. The orthosteric center of one protomer that modulates binding centers of the other protomers within an oligomer is also an unexpected allosteric site. Furthermore, another partner protein can also produce these effects, acting as an unexpected allosteric modulator. Areas covered: This review summarizes both classical and non-classical allosterism. The authors focus on G protein-coupled receptor (GPCR) oligomers as a paradigm of allosteric molecules. Moreover, they show several examples of unexpected allosteric sites such as hidden allosteric sites in a protomer that appear after the interaction with other molecules and the allosterism exerted between orthosteric sites within GPCR oligomer, emphasizing on the allosteric modulations that can occur between binding sites. Expert opinion: The study of these new non-classical allosteric sites will expand the diversity of allosteric control on the function of orthosteric sites within proteins, whether GPCRs or other receptors, enzymes, or transporters. Moreover, the design of new drugs targeting these hidden allosteric sites or already known orthosteric sites acting as allosteric sites in protein homo- or hetero-oligomers will increase the therapeutic potential of allosterism.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/225750
url https://hdl.handle.net/2445/225750
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1080/17460441.2022.2085684
Expert Opinion on Drug Discovery, 2022, vol. 17, num.8, p. 897-923
https://doi.org/10.1080/17460441.2022.2085684
dc.rights.none.fl_str_mv (c) Informa Healthcare, 2022
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Informa Healthcare, 2022
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Informa Healthcare
publisher.none.fl_str_mv Informa Healthcare
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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