Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin
- Autores
- Zhang, Hengxi; Modenutti, Carlos Pablo; Nekkanti, Yelha Phani Kumar; Denis, Maxime; Bermejo, Iris A.; Lefèbre, Jonathan; Che, Kateryna; Kim, Dongyoon; Kagelmacher, Marten; Kurzbach, Dennis; Nazaré, Marc; Rademacher, Christoph
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Langerin is a mammalian C-type lectin expressed on Langerhans cells in the skin. As an innate immune cell receptor, Langerin is involved in coordinating innate and adaptive immune responses against various incoming threats. We have previously reported a series of thiazolopyrimidines as murine Langerin ligands. Prompted by the observation that its human homologue exhibits different binding specificities for these small molecules, we report here our investigations to define their exact binding site. By using structural comparison and molecular dynamics simulations, we showed that the nonconserved short loops have a high degree of conformational flexibility between the human and murine homologues. Sequence analysis and mutational studies indicated that a pair of residues are essential for the recognition of the thiazolopyrimidines. Taking solvent paramagnetic relaxation enhancement NMR studies together with a series of peptides occupying the same site, we could define the cleft between the short and long loops as the allosteric binding site for these aromatic heterocycles.
Fil: Zhang, Hengxi. Vienna University of Technology; Austria
Fil: Modenutti, Carlos Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Nekkanti, Yelha Phani Kumar. Berlin Institute of Health; Alemania
Fil: Denis, Maxime. Vienna University of Technology; Austria
Fil: Bermejo, Iris A.. Vienna University of Technology; Austria
Fil: Lefèbre, Jonathan. Vienna University of Technology; Austria
Fil: Che, Kateryna. Vienna University of Technology; Austria
Fil: Kim, Dongyoon. Vienna University of Technology; Austria
Fil: Kagelmacher, Marten. Freie Universität Berlin; Alemania
Fil: Kurzbach, Dennis. Vienna University of Technology; Austria
Fil: Nazaré, Marc. Vienna University of Technology; Austria
Fil: Rademacher, Christoph. Vienna University of Technology; Austria - Materia
- C-type lectin
- Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/267772
Ver los metadatos del registro completo
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Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin LangerinZhang, HengxiModenutti, Carlos PabloNekkanti, Yelha Phani KumarDenis, MaximeBermejo, Iris A.Lefèbre, JonathanChe, KaterynaKim, DongyoonKagelmacher, MartenKurzbach, DennisNazaré, MarcRademacher, ChristophC-type lectinhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Langerin is a mammalian C-type lectin expressed on Langerhans cells in the skin. As an innate immune cell receptor, Langerin is involved in coordinating innate and adaptive immune responses against various incoming threats. We have previously reported a series of thiazolopyrimidines as murine Langerin ligands. Prompted by the observation that its human homologue exhibits different binding specificities for these small molecules, we report here our investigations to define their exact binding site. By using structural comparison and molecular dynamics simulations, we showed that the nonconserved short loops have a high degree of conformational flexibility between the human and murine homologues. Sequence analysis and mutational studies indicated that a pair of residues are essential for the recognition of the thiazolopyrimidines. Taking solvent paramagnetic relaxation enhancement NMR studies together with a series of peptides occupying the same site, we could define the cleft between the short and long loops as the allosteric binding site for these aromatic heterocycles.Fil: Zhang, Hengxi. Vienna University of Technology; AustriaFil: Modenutti, Carlos Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Nekkanti, Yelha Phani Kumar. Berlin Institute of Health; AlemaniaFil: Denis, Maxime. Vienna University of Technology; AustriaFil: Bermejo, Iris A.. Vienna University of Technology; AustriaFil: Lefèbre, Jonathan. Vienna University of Technology; AustriaFil: Che, Kateryna. Vienna University of Technology; AustriaFil: Kim, Dongyoon. Vienna University of Technology; AustriaFil: Kagelmacher, Marten. Freie Universität Berlin; AlemaniaFil: Kurzbach, Dennis. Vienna University of Technology; AustriaFil: Nazaré, Marc. Vienna University of Technology; AustriaFil: Rademacher, Christoph. Vienna University of Technology; AustriaAmerican Chemical Society2022-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/267772Zhang, Hengxi; Modenutti, Carlos Pablo; Nekkanti, Yelha Phani Kumar; Denis, Maxime; Bermejo, Iris A.; et al.; Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin; American Chemical Society; ACS Chemical Biology; 17; 10; 9-2022; 2728-27331554-8929CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acschembio.2c00626info:eu-repo/semantics/altIdentifier/doi/10.1021/acschembio.2c00626info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:07Zoai:ri.conicet.gov.ar:11336/267772instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:36:07.651CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
title |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
spellingShingle |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin Zhang, Hengxi C-type lectin |
title_short |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
title_full |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
title_fullStr |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
title_full_unstemmed |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
title_sort |
Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin |
dc.creator.none.fl_str_mv |
Zhang, Hengxi Modenutti, Carlos Pablo Nekkanti, Yelha Phani Kumar Denis, Maxime Bermejo, Iris A. Lefèbre, Jonathan Che, Kateryna Kim, Dongyoon Kagelmacher, Marten Kurzbach, Dennis Nazaré, Marc Rademacher, Christoph |
author |
Zhang, Hengxi |
author_facet |
Zhang, Hengxi Modenutti, Carlos Pablo Nekkanti, Yelha Phani Kumar Denis, Maxime Bermejo, Iris A. Lefèbre, Jonathan Che, Kateryna Kim, Dongyoon Kagelmacher, Marten Kurzbach, Dennis Nazaré, Marc Rademacher, Christoph |
author_role |
author |
author2 |
Modenutti, Carlos Pablo Nekkanti, Yelha Phani Kumar Denis, Maxime Bermejo, Iris A. Lefèbre, Jonathan Che, Kateryna Kim, Dongyoon Kagelmacher, Marten Kurzbach, Dennis Nazaré, Marc Rademacher, Christoph |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
C-type lectin |
topic |
C-type lectin |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Langerin is a mammalian C-type lectin expressed on Langerhans cells in the skin. As an innate immune cell receptor, Langerin is involved in coordinating innate and adaptive immune responses against various incoming threats. We have previously reported a series of thiazolopyrimidines as murine Langerin ligands. Prompted by the observation that its human homologue exhibits different binding specificities for these small molecules, we report here our investigations to define their exact binding site. By using structural comparison and molecular dynamics simulations, we showed that the nonconserved short loops have a high degree of conformational flexibility between the human and murine homologues. Sequence analysis and mutational studies indicated that a pair of residues are essential for the recognition of the thiazolopyrimidines. Taking solvent paramagnetic relaxation enhancement NMR studies together with a series of peptides occupying the same site, we could define the cleft between the short and long loops as the allosteric binding site for these aromatic heterocycles. Fil: Zhang, Hengxi. Vienna University of Technology; Austria Fil: Modenutti, Carlos Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Nekkanti, Yelha Phani Kumar. Berlin Institute of Health; Alemania Fil: Denis, Maxime. Vienna University of Technology; Austria Fil: Bermejo, Iris A.. Vienna University of Technology; Austria Fil: Lefèbre, Jonathan. Vienna University of Technology; Austria Fil: Che, Kateryna. Vienna University of Technology; Austria Fil: Kim, Dongyoon. Vienna University of Technology; Austria Fil: Kagelmacher, Marten. Freie Universität Berlin; Alemania Fil: Kurzbach, Dennis. Vienna University of Technology; Austria Fil: Nazaré, Marc. Vienna University of Technology; Austria Fil: Rademacher, Christoph. Vienna University of Technology; Austria |
description |
Langerin is a mammalian C-type lectin expressed on Langerhans cells in the skin. As an innate immune cell receptor, Langerin is involved in coordinating innate and adaptive immune responses against various incoming threats. We have previously reported a series of thiazolopyrimidines as murine Langerin ligands. Prompted by the observation that its human homologue exhibits different binding specificities for these small molecules, we report here our investigations to define their exact binding site. By using structural comparison and molecular dynamics simulations, we showed that the nonconserved short loops have a high degree of conformational flexibility between the human and murine homologues. Sequence analysis and mutational studies indicated that a pair of residues are essential for the recognition of the thiazolopyrimidines. Taking solvent paramagnetic relaxation enhancement NMR studies together with a series of peptides occupying the same site, we could define the cleft between the short and long loops as the allosteric binding site for these aromatic heterocycles. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/267772 Zhang, Hengxi; Modenutti, Carlos Pablo; Nekkanti, Yelha Phani Kumar; Denis, Maxime; Bermejo, Iris A.; et al.; Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin; American Chemical Society; ACS Chemical Biology; 17; 10; 9-2022; 2728-2733 1554-8929 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/267772 |
identifier_str_mv |
Zhang, Hengxi; Modenutti, Carlos Pablo; Nekkanti, Yelha Phani Kumar; Denis, Maxime; Bermejo, Iris A.; et al.; Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin; American Chemical Society; ACS Chemical Biology; 17; 10; 9-2022; 2728-2733 1554-8929 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acschembio.2c00626 info:eu-repo/semantics/altIdentifier/doi/10.1021/acschembio.2c00626 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613130150215680 |
score |
13.070432 |