Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme

Autores
Baltrusch, Simone; Francini, Flavio; Lenzen, Sigurd; Tiedge, Markus
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The glucokinase regulatory protein (GRP) plays a pivotal role in the regulation of metabolic flux in liver by the glucose-phosphorylating enzyme glucokinase. Random peptide phage display library screening for binding partners of GRP allowed the identification of an asparagine-leucine consensus motif. Asparagine-leucine motifs of glucokinase located in the hinge region, as well as in the large domain, were changed by site-directed mutagenesis. The L58R/N204Y and the L309R/N313Y glucokinase mutants showed a significantly reduced interaction with GRP. The L355R/N350Y mutant had a fivefold-higher binding affinity for GRP than wild-type glucokinase. Imaging of glucokinase and GRP fluorescence fusion proteins revealed that the L58R/N204Y glucokinase mutant lacked glucose-dependent translocation by GRP, whereas the L355R/N350Y glucokinase mutant was trapped in the nucleus due to high affinity for GRP. The results indicate that the L58/N204 motif in the hinge region confers binding to GRP, while the L355/N350 motif may modulate the binding affinity for GRP. This latter motif is part of the alpha10 helix of glucokinase and accessible to GRP in the free and complex conformation.
Fil: Baltrusch, Simone. Medizinische Hochschule Hannover; Alemania
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina. Medizinische Hochschule Hannover; Alemania
Fil: Lenzen, Sigurd. Medizinische Hochschule Hannover; Alemania
Fil: Tiedge, Markus. Medizinische Hochschule Hannover; Alemania
Materia
METABOLISM
GLUCOKINASE
GRP
PROTEINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/142378
Acceder
id CONICETDig_8b935f8e5690db4c93e03d5920379070
oai_identifier_str oai:ri.conicet.gov.ar:11336/142378
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzymeBaltrusch, SimoneFrancini, FlavioLenzen, SigurdTiedge, MarkusMETABOLISMGLUCOKINASEGRPPROTEINShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The glucokinase regulatory protein (GRP) plays a pivotal role in the regulation of metabolic flux in liver by the glucose-phosphorylating enzyme glucokinase. Random peptide phage display library screening for binding partners of GRP allowed the identification of an asparagine-leucine consensus motif. Asparagine-leucine motifs of glucokinase located in the hinge region, as well as in the large domain, were changed by site-directed mutagenesis. The L58R/N204Y and the L309R/N313Y glucokinase mutants showed a significantly reduced interaction with GRP. The L355R/N350Y mutant had a fivefold-higher binding affinity for GRP than wild-type glucokinase. Imaging of glucokinase and GRP fluorescence fusion proteins revealed that the L58R/N204Y glucokinase mutant lacked glucose-dependent translocation by GRP, whereas the L355R/N350Y glucokinase mutant was trapped in the nucleus due to high affinity for GRP. The results indicate that the L58/N204 motif in the hinge region confers binding to GRP, while the L355/N350 motif may modulate the binding affinity for GRP. This latter motif is part of the alpha10 helix of glucokinase and accessible to GRP in the free and complex conformation.Fil: Baltrusch, Simone. Medizinische Hochschule Hannover; AlemaniaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina. Medizinische Hochschule Hannover; AlemaniaFil: Lenzen, Sigurd. Medizinische Hochschule Hannover; AlemaniaFil: Tiedge, Markus. Medizinische Hochschule Hannover; AlemaniaAmerican Diabetes Association2005-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/142378Baltrusch, Simone; Francini, Flavio; Lenzen, Sigurd; Tiedge, Markus; Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme; American Diabetes Association; Diabetes; 54; 10; 10-2005; 2829-28370012-1797CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://diabetes.diabetesjournals.org/content/54/10/2829.longinfo:eu-repo/semantics/altIdentifier/doi/10.2337/diabetes.54.10.2829info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:29Zoai:ri.conicet.gov.ar:11336/142378instacron: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:34982025-09-10 13:01:29.599CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
title Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
spellingShingle Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
Baltrusch, Simone
METABOLISM
GLUCOKINASE
GRP
PROTEINS
title_short Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
title_full Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
title_fullStr Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
title_full_unstemmed Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
title_sort Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme
dc.creator.none.fl_str_mv Baltrusch, Simone
Francini, Flavio
Lenzen, Sigurd
Tiedge, Markus
author Baltrusch, Simone
author_facet Baltrusch, Simone
Francini, Flavio
Lenzen, Sigurd
Tiedge, Markus
author_role author
author2 Francini, Flavio
Lenzen, Sigurd
Tiedge, Markus
author2_role author
author
author
dc.subject.none.fl_str_mv METABOLISM
GLUCOKINASE
GRP
PROTEINS
topic METABOLISM
GLUCOKINASE
GRP
PROTEINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The glucokinase regulatory protein (GRP) plays a pivotal role in the regulation of metabolic flux in liver by the glucose-phosphorylating enzyme glucokinase. Random peptide phage display library screening for binding partners of GRP allowed the identification of an asparagine-leucine consensus motif. Asparagine-leucine motifs of glucokinase located in the hinge region, as well as in the large domain, were changed by site-directed mutagenesis. The L58R/N204Y and the L309R/N313Y glucokinase mutants showed a significantly reduced interaction with GRP. The L355R/N350Y mutant had a fivefold-higher binding affinity for GRP than wild-type glucokinase. Imaging of glucokinase and GRP fluorescence fusion proteins revealed that the L58R/N204Y glucokinase mutant lacked glucose-dependent translocation by GRP, whereas the L355R/N350Y glucokinase mutant was trapped in the nucleus due to high affinity for GRP. The results indicate that the L58/N204 motif in the hinge region confers binding to GRP, while the L355/N350 motif may modulate the binding affinity for GRP. This latter motif is part of the alpha10 helix of glucokinase and accessible to GRP in the free and complex conformation.
Fil: Baltrusch, Simone. Medizinische Hochschule Hannover; Alemania
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina. Medizinische Hochschule Hannover; Alemania
Fil: Lenzen, Sigurd. Medizinische Hochschule Hannover; Alemania
Fil: Tiedge, Markus. Medizinische Hochschule Hannover; Alemania
description The glucokinase regulatory protein (GRP) plays a pivotal role in the regulation of metabolic flux in liver by the glucose-phosphorylating enzyme glucokinase. Random peptide phage display library screening for binding partners of GRP allowed the identification of an asparagine-leucine consensus motif. Asparagine-leucine motifs of glucokinase located in the hinge region, as well as in the large domain, were changed by site-directed mutagenesis. The L58R/N204Y and the L309R/N313Y glucokinase mutants showed a significantly reduced interaction with GRP. The L355R/N350Y mutant had a fivefold-higher binding affinity for GRP than wild-type glucokinase. Imaging of glucokinase and GRP fluorescence fusion proteins revealed that the L58R/N204Y glucokinase mutant lacked glucose-dependent translocation by GRP, whereas the L355R/N350Y glucokinase mutant was trapped in the nucleus due to high affinity for GRP. The results indicate that the L58/N204 motif in the hinge region confers binding to GRP, while the L355/N350 motif may modulate the binding affinity for GRP. This latter motif is part of the alpha10 helix of glucokinase and accessible to GRP in the free and complex conformation.
publishDate 2005
dc.date.none.fl_str_mv 2005-10
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/11336/142378
Baltrusch, Simone; Francini, Flavio; Lenzen, Sigurd; Tiedge, Markus; Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme; American Diabetes Association; Diabetes; 54; 10; 10-2005; 2829-2837
0012-1797
CONICET Digital
CONICET
url http://hdl.handle.net/11336/142378
identifier_str_mv Baltrusch, Simone; Francini, Flavio; Lenzen, Sigurd; Tiedge, Markus; Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme; American Diabetes Association; Diabetes; 54; 10; 10-2005; 2829-2837
0012-1797
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://diabetes.diabetesjournals.org/content/54/10/2829.long
info:eu-repo/semantics/altIdentifier/doi/10.2337/diabetes.54.10.2829
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
dc.publisher.none.fl_str_mv American Diabetes Association
publisher.none.fl_str_mv American Diabetes Association
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_ 1842979952109027328
score 12.993085

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