One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures.
Schools of Biological and Chemical Sciences and Engineering and Computer Science, University of Exeter, Washington Singer Laboratories, Prince of Wales Road, Exeter, UK. Fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) are associated to the same mutation at codon 178 but differen...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wiley Interscience
2005
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| Online Access: | http://eprints.utm.my/491/ http://eprints.utm.my/491/1/OneGeneTwoDiseasesandThreeConformations.pdf |
| _version_ | 1848889932851970048 |
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| author | Shamsir, Mohd Shahir Dalby, Andrew |
| author_facet | Shamsir, Mohd Shahir Dalby, Andrew |
| author_sort | Shamsir, Mohd Shahir |
| building | UTeM Institutional Repository |
| collection | Online Access |
| description | Schools of Biological and Chemical Sciences and Engineering and Computer Science, University of Exeter, Washington Singer Laboratories, Prince of Wales Road, Exeter, UK.
Fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) are associated to the same mutation at codon 178 but differentiate into clinicopathologically distinct diseases determined by this mutation and a naturally occurring methionine-valine polymorphism at codon 129 of the prion protein gene. It has been suggested that the clinical and pathological difference between FFI and CJD is caused by different conformations of the prion protein. Using molecular dynamics (MD), we investigated the effect of the mutation at codon 178 and the polymorphism at codon 129 on prion protein dynamics and conformation at normal and elevated temperatures. Four model structures were examined with a focus on their dynamics and conformational changes. The results showed differences in stability and dynamics between polymorphic variants. Methionine variants demonstrated a higher stability than valine variants. Elongation of existing beta-sheets and formation of new beta-sheets was found to occur more readily in valine polymorphic variants. We also discovered the inhibitory effect of proline residue on existing beta-sheet elongation |
| first_indexed | 2025-11-15T20:34:02Z |
| format | Article |
| id | utm-491 |
| institution | Universiti Teknologi Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T20:34:02Z |
| publishDate | 2005 |
| publisher | Wiley Interscience |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | utm-4912010-06-01T02:45:01Z http://eprints.utm.my/491/ One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. Shamsir, Mohd Shahir Dalby, Andrew Q Science (General) QH301 Biology Schools of Biological and Chemical Sciences and Engineering and Computer Science, University of Exeter, Washington Singer Laboratories, Prince of Wales Road, Exeter, UK. Fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) are associated to the same mutation at codon 178 but differentiate into clinicopathologically distinct diseases determined by this mutation and a naturally occurring methionine-valine polymorphism at codon 129 of the prion protein gene. It has been suggested that the clinical and pathological difference between FFI and CJD is caused by different conformations of the prion protein. Using molecular dynamics (MD), we investigated the effect of the mutation at codon 178 and the polymorphism at codon 129 on prion protein dynamics and conformation at normal and elevated temperatures. Four model structures were examined with a focus on their dynamics and conformational changes. The results showed differences in stability and dynamics between polymorphic variants. Methionine variants demonstrated a higher stability than valine variants. Elongation of existing beta-sheets and formation of new beta-sheets was found to occur more readily in valine polymorphic variants. We also discovered the inhibitory effect of proline residue on existing beta-sheet elongation Wiley Interscience 2005-02-28 Article PeerReviewed application/pdf en http://eprints.utm.my/491/1/OneGeneTwoDiseasesandThreeConformations.pdf Shamsir, Mohd Shahir and Dalby, Andrew (2005) One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. Proteins: Structure, Function, and Bioinformatics, 59 (2). pp. 275-290. http://www3.interscience.wiley.com/cgi-bin/abstract/109932329/ABSTRACT 10.1002/prot.20401 |
| spellingShingle | Q Science (General) QH301 Biology Shamsir, Mohd Shahir Dalby, Andrew One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title | One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title_full | One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title_fullStr | One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title_full_unstemmed | One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title_short | One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| title_sort | one gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. |
| topic | Q Science (General) QH301 Biology |
| url | http://eprints.utm.my/491/ http://eprints.utm.my/491/ http://eprints.utm.my/491/ http://eprints.utm.my/491/1/OneGeneTwoDiseasesandThreeConformations.pdf |