| Model of the 3-D structure of the GLUT3 glucose transporter and molecular dynamics simulation of glucose transport. | |
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MedLine Citation:
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PMID: 11170207 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A molecular model of the three-dimensional (3-D) structure of the glucose transport protein, GLUT3, has been derived by homology modeling. The model was built on the basis of structural data from the MscL protein, which is a mechanosensitive ion channel, and general insights from aquaporin (a water permeation pore). Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were selected from the protein databank, and amino (N)- and carboxy (C)-terminal ends of the protein were generated as random coil structures. The model was then subjected to energy minimization and molecular dynamics simulations in the presence of bound substrate (D-glucose). In the proposed structure of GLUT3, the 12 transmembrane (TM) helices form a right-hand barrel with a central hydrophilic pore. The pore is shaped like a funnel with dimensions of approximately 5-6 A by 8 A at its narrowest point. A network of polar and aromatic amino acids line the pore region and may facilitate the movement of glucose along the channel. A putative binding site for inhibitory ligands, such as forskolin and cytochalasin B, was identified on an intracellular aspect of the protein. Molecular dynamics studies showed that changes in the tilt and flexibility of key TM helices may modulate the opening of the pore to effect glucose transport. The proposed structure of GLUT3 may prove useful in guiding future experiments aimed at more precisely defining various functional regions of the transporter and may encourage efforts to develop models of other complex membrane proteins. |
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Authors:
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D S Dwyer |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Proteins Volume: 42 ISSN: 0887-3585 ISO Abbreviation: Proteins Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-04-26 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8700181 Medline TA: Proteins Country: United States |
Other Details:
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Languages: eng Pagination: 531-41 Citation Subset: IM |
Copyright Information:
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Copyright 2001 Wiley-Liss, Inc. |
Affiliation:
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Departments of Psychiatry and Pharmacology, Louisiana State University Health Sciences Center, Shreveport 71130, USA. ddwyer@lsuhsc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Binding Sites Biological Transport Biophysical Phenomena Biophysics Escherichia coli Proteins* Glucose / metabolism* Glucose Transporter Type 3 Humans Ion Channels / chemistry Models, Molecular Molecular Sequence Data Molecular Structure Monosaccharide Transport Proteins / chemistry*, genetics, metabolism Nerve Tissue Proteins* Protein Structure, Secondary Protein Structure, Tertiary Sequence Homology, Amino Acid Thermodynamics Water / chemistry |
| Chemical | |
Reg. No./Substance:
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0/Escherichia coli Proteins; 0/Glucose Transporter Type 3; 0/Ion Channels; 0/Monosaccharide Transport Proteins; 0/MscL protein, E coli; 0/Nerve Tissue Proteins; 0/SLC2A3 protein, human; 50-99-7/Glucose; 7732-18-5/Water |
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