Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite
- Autores
- Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Enriz, Ricardo Daniel; Baldoni, Hector Armando
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- A molecular modeling study giving structural, functional, and mutagenesis insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite is reported. Our results allow extending experimental data resulting from X-ray dif- fraction experiments in order to examine unknown aspects for the Fab-BACE1 recognition and its binding mode. Thus, the study performed here allows extending the inherently static nature of crystallographic structures in order to gain a deeper understanding of the structural and dynamical basis at the atomic level. The characteristics and strength of the interatomic interactions involved in the immune complex formation are exhaustively analyzed. The results might explain how the anti-BACE1 Fab fragment and other BACE1 exosite binders are capable to produce an allosteric modulation of the BACE1 activity. Our site-directed mutagenesis study indicated that the functional anti-BACE1 paratope, residues Tyr32 (H1), Trp50 (H2), Arg98 (H3), Phe101 (H3), Trp104 (H3) and Tyr94 (L3), strongly dominates the binding ener- getics with the BACE1 exosite. The mutational studies described in this work might accelerate the development of new BACE1 exosite binders with interesting pharmacological activity.
Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina
Fil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Matemática Aplicada de San Luis; Argentina. Universidad Nacional de San Luis; Argentina - Materia
-
Bace1
Alzheimer
Immune Complex
Allosteric Control - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/18557
Ver los metadatos del registro completo
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spelling |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exositeGutierrez, Lucas JoelAndujar, Sebastian AntonioEnriz, Ricardo DanielBaldoni, Hector ArmandoBace1AlzheimerImmune ComplexAllosteric Controlhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A molecular modeling study giving structural, functional, and mutagenesis insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite is reported. Our results allow extending experimental data resulting from X-ray dif- fraction experiments in order to examine unknown aspects for the Fab-BACE1 recognition and its binding mode. Thus, the study performed here allows extending the inherently static nature of crystallographic structures in order to gain a deeper understanding of the structural and dynamical basis at the atomic level. The characteristics and strength of the interatomic interactions involved in the immune complex formation are exhaustively analyzed. The results might explain how the anti-BACE1 Fab fragment and other BACE1 exosite binders are capable to produce an allosteric modulation of the BACE1 activity. Our site-directed mutagenesis study indicated that the functional anti-BACE1 paratope, residues Tyr32 (H1), Trp50 (H2), Arg98 (H3), Phe101 (H3), Trp104 (H3) and Tyr94 (L3), strongly dominates the binding ener- getics with the BACE1 exosite. The mutational studies described in this work might accelerate the development of new BACE1 exosite binders with interesting pharmacological activity.Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Matemática Aplicada de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaTaylor & Francis2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18557Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Enriz, Ricardo Daniel; Baldoni, Hector Armando; Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite; Taylor & Francis; Journal Of Biomolecular Structure & Dynamics; 32; 9; 9-2014; 1421-14330739-1102enginfo:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.1080/07391102.2013.821024?journalCode=tbsd20info:eu-repo/semantics/altIdentifier/doi/10.1080/07391102.2013.821024info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:10Zoai:ri.conicet.gov.ar:11336/18557instacron: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 10:44:10.507CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
title |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
spellingShingle |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite Gutierrez, Lucas Joel Bace1 Alzheimer Immune Complex Allosteric Control |
title_short |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
title_full |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
title_fullStr |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
title_full_unstemmed |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
title_sort |
Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite |
dc.creator.none.fl_str_mv |
Gutierrez, Lucas Joel Andujar, Sebastian Antonio Enriz, Ricardo Daniel Baldoni, Hector Armando |
author |
Gutierrez, Lucas Joel |
author_facet |
Gutierrez, Lucas Joel Andujar, Sebastian Antonio Enriz, Ricardo Daniel Baldoni, Hector Armando |
author_role |
author |
author2 |
Andujar, Sebastian Antonio Enriz, Ricardo Daniel Baldoni, Hector Armando |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Bace1 Alzheimer Immune Complex Allosteric Control |
topic |
Bace1 Alzheimer Immune Complex Allosteric Control |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
A molecular modeling study giving structural, functional, and mutagenesis insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite is reported. Our results allow extending experimental data resulting from X-ray dif- fraction experiments in order to examine unknown aspects for the Fab-BACE1 recognition and its binding mode. Thus, the study performed here allows extending the inherently static nature of crystallographic structures in order to gain a deeper understanding of the structural and dynamical basis at the atomic level. The characteristics and strength of the interatomic interactions involved in the immune complex formation are exhaustively analyzed. The results might explain how the anti-BACE1 Fab fragment and other BACE1 exosite binders are capable to produce an allosteric modulation of the BACE1 activity. Our site-directed mutagenesis study indicated that the functional anti-BACE1 paratope, residues Tyr32 (H1), Trp50 (H2), Arg98 (H3), Phe101 (H3), Trp104 (H3) and Tyr94 (L3), strongly dominates the binding ener- getics with the BACE1 exosite. The mutational studies described in this work might accelerate the development of new BACE1 exosite binders with interesting pharmacological activity. Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina Fil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Matemática Aplicada de San Luis; Argentina. Universidad Nacional de San Luis; Argentina |
description |
A molecular modeling study giving structural, functional, and mutagenesis insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite is reported. Our results allow extending experimental data resulting from X-ray dif- fraction experiments in order to examine unknown aspects for the Fab-BACE1 recognition and its binding mode. Thus, the study performed here allows extending the inherently static nature of crystallographic structures in order to gain a deeper understanding of the structural and dynamical basis at the atomic level. The characteristics and strength of the interatomic interactions involved in the immune complex formation are exhaustively analyzed. The results might explain how the anti-BACE1 Fab fragment and other BACE1 exosite binders are capable to produce an allosteric modulation of the BACE1 activity. Our site-directed mutagenesis study indicated that the functional anti-BACE1 paratope, residues Tyr32 (H1), Trp50 (H2), Arg98 (H3), Phe101 (H3), Trp104 (H3) and Tyr94 (L3), strongly dominates the binding ener- getics with the BACE1 exosite. The mutational studies described in this work might accelerate the development of new BACE1 exosite binders with interesting pharmacological activity. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-09 |
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/11336/18557 Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Enriz, Ricardo Daniel; Baldoni, Hector Armando; Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite; Taylor & Francis; Journal Of Biomolecular Structure & Dynamics; 32; 9; 9-2014; 1421-1433 0739-1102 |
url |
http://hdl.handle.net/11336/18557 |
identifier_str_mv |
Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Enriz, Ricardo Daniel; Baldoni, Hector Armando; Structural and functional insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite; Taylor & Francis; Journal Of Biomolecular Structure & Dynamics; 32; 9; 9-2014; 1421-1433 0739-1102 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.1080/07391102.2013.821024?journalCode=tbsd20 info:eu-repo/semantics/altIdentifier/doi/10.1080/07391102.2013.821024 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Taylor & Francis |
publisher.none.fl_str_mv |
Taylor & Francis |
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 |
_version_ |
1844614478465859584 |
score |
13.070432 |