Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype
<ul><li>The prevalence of homocystinuria in Qatar is 1:1800, mainly due to a founder missense mutation p.R336C.</li><li>The cystathionine beta-synthase (CBS) R336C mutant was bacterially expressed, purified and its molecular properties were compared to CBS wild type (WT) reco...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2022
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| الموضوعات: | |
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| _version_ | 1864513535795527680 |
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| author | Duaa W. Al-Sadeq (10976754) |
| author2 | Angelos Thanassoulas (2822861) Zeyaul Islam (5867387) Prasanna Kolatkar (7532792) Nader Al-Dewik (4166527) Bared Safieh-Garabedian (3554684) Gheyath K. Nasrallah (9200525) Michail Nomikos (17563188) |
| author2_role | author author author author author author author |
| author_facet | Duaa W. Al-Sadeq (10976754) Angelos Thanassoulas (2822861) Zeyaul Islam (5867387) Prasanna Kolatkar (7532792) Nader Al-Dewik (4166527) Bared Safieh-Garabedian (3554684) Gheyath K. Nasrallah (9200525) Michail Nomikos (17563188) |
| author_role | author |
| dc.creator.none.fl_str_mv | Duaa W. Al-Sadeq (10976754) Angelos Thanassoulas (2822861) Zeyaul Islam (5867387) Prasanna Kolatkar (7532792) Nader Al-Dewik (4166527) Bared Safieh-Garabedian (3554684) Gheyath K. Nasrallah (9200525) Michail Nomikos (17563188) |
| dc.date.none.fl_str_mv | 2022-07-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.bbagen.2022.130148 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Pyridoxine_non-responsive_p_R336C_mutation_alters_the_molecular_properties_of_cystathionine_beta-synthase_leading_to_severe_homocystinuria_phenotype/24745713 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Homocystinuria Cystathionine beta-synthase R336C mutation Biochemical characterization Biophysical characterization |
| dc.title.none.fl_str_mv | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <ul><li>The prevalence of homocystinuria in Qatar is 1:1800, mainly due to a founder missense mutation p.R336C.</li><li>The cystathionine beta-synthase (CBS) R336C mutant was bacterially expressed, purified and its molecular properties were compared to CBS wild type (WT) recombinant protein.</li><li>Our data revealed that p.R336C mutation results in a dramatic reduction (∼86%) of CBS enzymatic activity.</li><li>Circular Dichroism experiments suggested that the p.R336C mutation does not significantly alter the secondary structure of the CBS protein.</li><li>CD spectra also revealed distinct differences in the thermal unfolding mechanisms of CBS WT and R336C mutant protein species.</li><li>Chemical denaturation experiments indicated that the WT CBS protein is thermodynamically more stable than the R336C mutant, suggesting a destabilizing effect of the p.R336C mutation.</li><li>This study provides mechanistic insight into the pathogenicity of the p.R336C mutation that leads to a severe homocystinuria phenotype.</li></ul><h2>Other Information</h2><p dir="ltr">Published in: Biochimica et Biophysica Acta (BBA) - General Subjects<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.bbagen.2022.130148" target="_blank">https://dx.doi.org/10.1016/j.bbagen.2022.130148</a></p><p dir="ltr">Additional institutions affiliated with: Hamad Medical Corporation, Hamad General Hospital - HMC, Women's Wellness and Research Center - HMC, Interim Translational Research Institute - HMC</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9f49f5f6b61bfe7db4d5c577383e1499 |
| identifier_str_mv | 10.1016/j.bbagen.2022.130148 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24745713 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotypeDuaa W. Al-Sadeq (10976754)Angelos Thanassoulas (2822861)Zeyaul Islam (5867387)Prasanna Kolatkar (7532792)Nader Al-Dewik (4166527)Bared Safieh-Garabedian (3554684)Gheyath K. Nasrallah (9200525)Michail Nomikos (17563188)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesMedical biochemistry and metabolomicsMedical physiologyHomocystinuriaCystathionine beta-synthaseR336C mutationBiochemical characterizationBiophysical characterization<ul><li>The prevalence of homocystinuria in Qatar is 1:1800, mainly due to a founder missense mutation p.R336C.</li><li>The cystathionine beta-synthase (CBS) R336C mutant was bacterially expressed, purified and its molecular properties were compared to CBS wild type (WT) recombinant protein.</li><li>Our data revealed that p.R336C mutation results in a dramatic reduction (∼86%) of CBS enzymatic activity.</li><li>Circular Dichroism experiments suggested that the p.R336C mutation does not significantly alter the secondary structure of the CBS protein.</li><li>CD spectra also revealed distinct differences in the thermal unfolding mechanisms of CBS WT and R336C mutant protein species.</li><li>Chemical denaturation experiments indicated that the WT CBS protein is thermodynamically more stable than the R336C mutant, suggesting a destabilizing effect of the p.R336C mutation.</li><li>This study provides mechanistic insight into the pathogenicity of the p.R336C mutation that leads to a severe homocystinuria phenotype.</li></ul><h2>Other Information</h2><p dir="ltr">Published in: Biochimica et Biophysica Acta (BBA) - General Subjects<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.bbagen.2022.130148" target="_blank">https://dx.doi.org/10.1016/j.bbagen.2022.130148</a></p><p dir="ltr">Additional institutions affiliated with: Hamad Medical Corporation, Hamad General Hospital - HMC, Women's Wellness and Research Center - HMC, Interim Translational Research Institute - HMC</p>2022-07-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.bbagen.2022.130148https://figshare.com/articles/journal_contribution/Pyridoxine_non-responsive_p_R336C_mutation_alters_the_molecular_properties_of_cystathionine_beta-synthase_leading_to_severe_homocystinuria_phenotype/24745713CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/247457132022-07-01T00:00:00Z |
| spellingShingle | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype Duaa W. Al-Sadeq (10976754) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Homocystinuria Cystathionine beta-synthase R336C mutation Biochemical characterization Biophysical characterization |
| status_str | publishedVersion |
| title | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| title_full | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| title_fullStr | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| title_full_unstemmed | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| title_short | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| title_sort | Pyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Homocystinuria Cystathionine beta-synthase R336C mutation Biochemical characterization Biophysical characterization |