A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites
Functional specificity of a protein is linked to its structure. A growing section of bioinformatics deals with the prediction and visualization of protein 3D structures. In homology modelling, a protein sequence with an unknown structure is aligned with sequences of known protein structures. By expl...
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| Format: | Article |
| Language: | English |
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De Gruyter
2007-02-01
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| Series: | Pteridines |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/pteridines.2007.18.1.79 |
| _version_ | 1818669072355688448 |
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| author | Wiltgen Marco Tilz Gernot P. |
| author_facet | Wiltgen Marco Tilz Gernot P. |
| author_sort | Wiltgen Marco |
| collection | DOAJ |
| description | Functional specificity of a protein is linked to its structure. A growing section of bioinformatics deals with the prediction and visualization of protein 3D structures. In homology modelling, a protein sequence with an unknown structure is aligned with sequences of known protein structures. By exploiting structural information from the known configurations, the new structure can be predicted. In this introductory paper, we will present the principles of homology modelling and demonstrate the method used, by determining the structure of the enzyme glutamic decarboxylase (GAD 65). This protein is an autoantigen involved in several human autoimmune diseases. We will illustrate the different steps in structure prediction of GAD 65 by use of two experimentally determined structures of pig kidney DOPA decarboxylase (one structure in complex with the inhibitor carbidopa) as templates. The resulting model of GAD 65 provides detailed information about the active site of the protein and selected epitopes. By analysis of the interactions between the DOPA decarboxylase with the inhibitor carbidopa, the residues of the GAD 65 active site can be identified via the sequence alignment between DOPA and GAD 65. The locations of known epitopes in the molecule are visualized in special representations giving insights into mechanisms of antigenicity. Hydrophobicity analysis gives first hints for the adherence ability of GAD 65 to the cell membrane. Homology modelling is at present one of the most efficient techniques to provide accurate structural models of proteins. It is expected that in few years, for every new determined protein sequence, at least one member with a known structure of the same protein family will be available, which will steadily increase the importance and applicability of homology modelling. |
| first_indexed | 2024-12-17T06:46:24Z |
| format | Article |
| id | doaj.art-da0613f3ca3d4bc898cefe62032ae9a8 |
| institution | Directory Open Access Journal |
| issn | 0933-4807 2195-4720 |
| language | English |
| last_indexed | 2024-12-17T06:46:24Z |
| publishDate | 2007-02-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Pteridines |
| spelling | doaj.art-da0613f3ca3d4bc898cefe62032ae9a82022-12-21T21:59:45ZengDe GruyterPteridines0933-48072195-47202007-02-01181799410.1515/pteridines.2007.18.1.79A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding SitesWiltgen Marco0Tilz Gernot P.1Wiltgen, Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, A-8036 Graz, Austria, Tel.: +43 316 385 3587; fax: +43 316 385 3590Clinical Immunology and Jean Dausset Laboratory, Medical University of Graz, Graz, AustriaFunctional specificity of a protein is linked to its structure. A growing section of bioinformatics deals with the prediction and visualization of protein 3D structures. In homology modelling, a protein sequence with an unknown structure is aligned with sequences of known protein structures. By exploiting structural information from the known configurations, the new structure can be predicted. In this introductory paper, we will present the principles of homology modelling and demonstrate the method used, by determining the structure of the enzyme glutamic decarboxylase (GAD 65). This protein is an autoantigen involved in several human autoimmune diseases. We will illustrate the different steps in structure prediction of GAD 65 by use of two experimentally determined structures of pig kidney DOPA decarboxylase (one structure in complex with the inhibitor carbidopa) as templates. The resulting model of GAD 65 provides detailed information about the active site of the protein and selected epitopes. By analysis of the interactions between the DOPA decarboxylase with the inhibitor carbidopa, the residues of the GAD 65 active site can be identified via the sequence alignment between DOPA and GAD 65. The locations of known epitopes in the molecule are visualized in special representations giving insights into mechanisms of antigenicity. Hydrophobicity analysis gives first hints for the adherence ability of GAD 65 to the cell membrane. Homology modelling is at present one of the most efficient techniques to provide accurate structural models of proteins. It is expected that in few years, for every new determined protein sequence, at least one member with a known structure of the same protein family will be available, which will steadily increase the importance and applicability of homology modelling.https://doi.org/10.1515/pteridines.2007.18.1.79homology modellingantigengad 65epitopesprotein structure visualization |
| spellingShingle | Wiltgen Marco Tilz Gernot P. A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites Pteridines homology modelling antigen gad 65 epitopes protein structure visualization |
| title | A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites |
| title_full | A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites |
| title_fullStr | A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites |
| title_full_unstemmed | A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites |
| title_short | A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites |
| title_sort | basic molecular analysis of the diabetic antigen gad by homology modelling principles of the method and understanding of antigenicity and binding sites |
| topic | homology modelling antigen gad 65 epitopes protein structure visualization |
| url | https://doi.org/10.1515/pteridines.2007.18.1.79 |
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