N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.
One of the proposed mechanisms of homocysteine toxicity in human is the modification of proteins by the metabolite of Hcy, homocysteine thilolactone (HTL). Incubation of proteins with HTL has earlier been shown to form covalent adducts with ε-amino group of lysine residues of protein (called N-homoc...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4281231?pdf=render |
| _version_ | 1819242761746907136 |
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| author | Gurumayum Suraj Sharma Tarun Kumar Laishram Rajendrakumar Singh |
| author_facet | Gurumayum Suraj Sharma Tarun Kumar Laishram Rajendrakumar Singh |
| author_sort | Gurumayum Suraj Sharma |
| collection | DOAJ |
| description | One of the proposed mechanisms of homocysteine toxicity in human is the modification of proteins by the metabolite of Hcy, homocysteine thilolactone (HTL). Incubation of proteins with HTL has earlier been shown to form covalent adducts with ε-amino group of lysine residues of protein (called N-homocysteinylation). It has been believed that protein N-homocysteinylation is the pathological hallmark of cardiovascular and neurodegenerative disorders as homocysteinylation induces structural and functional alterations in proteins. In the present study, reactivity of HTL towards proteins with different physico-chemical properties and hence their structural and functional alterations were studied using different spectroscopic approaches. We found that N-homocysteinylation has opposite consequences on acidic and basic proteins suggesting that pI of the protein determines the extent of homocysteinylation, and the structural and functional consequences due to homocysteinylation. Mechanistically, pI of protein determines the extent of N-homocysteinylation and the associated structural and functional alterations. The study suggests the role of HTL primarily targeting acidic proteins in eliciting its toxicity that could yield mechanistic insights for the associated neurodegeneration. |
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| format | Article |
| id | doaj.art-ec0067d159e4444db3813a5252d3abc0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:44:57Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec0067d159e4444db3813a5252d3abc02022-12-21T17:43:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11638610.1371/journal.pone.0116386N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.Gurumayum Suraj SharmaTarun KumarLaishram Rajendrakumar SinghOne of the proposed mechanisms of homocysteine toxicity in human is the modification of proteins by the metabolite of Hcy, homocysteine thilolactone (HTL). Incubation of proteins with HTL has earlier been shown to form covalent adducts with ε-amino group of lysine residues of protein (called N-homocysteinylation). It has been believed that protein N-homocysteinylation is the pathological hallmark of cardiovascular and neurodegenerative disorders as homocysteinylation induces structural and functional alterations in proteins. In the present study, reactivity of HTL towards proteins with different physico-chemical properties and hence their structural and functional alterations were studied using different spectroscopic approaches. We found that N-homocysteinylation has opposite consequences on acidic and basic proteins suggesting that pI of the protein determines the extent of homocysteinylation, and the structural and functional consequences due to homocysteinylation. Mechanistically, pI of protein determines the extent of N-homocysteinylation and the associated structural and functional alterations. The study suggests the role of HTL primarily targeting acidic proteins in eliciting its toxicity that could yield mechanistic insights for the associated neurodegeneration.http://europepmc.org/articles/PMC4281231?pdf=render |
| spellingShingle | Gurumayum Suraj Sharma Tarun Kumar Laishram Rajendrakumar Singh N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. PLoS ONE |
| title | N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. |
| title_full | N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. |
| title_fullStr | N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. |
| title_full_unstemmed | N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. |
| title_short | N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. |
| title_sort | n homocysteinylation induces different structural and functional consequences on acidic and basic proteins |
| url | http://europepmc.org/articles/PMC4281231?pdf=render |
| work_keys_str_mv | AT gurumayumsurajsharma nhomocysteinylationinducesdifferentstructuralandfunctionalconsequencesonacidicandbasicproteins AT tarunkumar nhomocysteinylationinducesdifferentstructuralandfunctionalconsequencesonacidicandbasicproteins AT laishramrajendrakumarsingh nhomocysteinylationinducesdifferentstructuralandfunctionalconsequencesonacidicandbasicproteins |