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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2005-9-27
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0012-1797
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2829-37
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16186382-Amino Acid Sequence,
pubmed-meshheading:16186382-Animals,
pubmed-meshheading:16186382-Asparagine,
pubmed-meshheading:16186382-Base Sequence,
pubmed-meshheading:16186382-Binding Sites,
pubmed-meshheading:16186382-COS Cells,
pubmed-meshheading:16186382-Carrier Proteins,
pubmed-meshheading:16186382-Cercopithecus aethiops,
pubmed-meshheading:16186382-Consensus Sequence,
pubmed-meshheading:16186382-Glucokinase,
pubmed-meshheading:16186382-Green Fluorescent Proteins,
pubmed-meshheading:16186382-Hepatocytes,
pubmed-meshheading:16186382-Humans,
pubmed-meshheading:16186382-Kinetics,
pubmed-meshheading:16186382-Leucine,
pubmed-meshheading:16186382-Microscopy, Fluorescence,
pubmed-meshheading:16186382-Models, Molecular,
pubmed-meshheading:16186382-Mutagenesis, Site-Directed,
pubmed-meshheading:16186382-Peptide Library,
pubmed-meshheading:16186382-Rats,
pubmed-meshheading:16186382-Rats, Wistar,
pubmed-meshheading:16186382-Recombinant Fusion Proteins,
pubmed-meshheading:16186382-Recombinant Proteins,
pubmed-meshheading:16186382-Structure-Activity Relationship,
pubmed-meshheading:16186382-Transfection,
pubmed-meshheading:16186382-Two-Hybrid System Techniques
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pubmed:year |
2005
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pubmed:articleTitle |
Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme.
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pubmed:affiliation |
Institute of Clinical Biochemistry, Hannover Medical School, D-30623 Hannover, Germany. baltrusch.simone@mh-hannover.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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