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N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.

ABSTRACT: 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 ?-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.

SUBMITTER: Sharma GS

PROVIDER: S-EPMC4281231 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.

Sharma Gurumayum Suraj GS Kumar Tarun T Singh Laishram Rajendrakumar LR

PloS one 20141231 12

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 funct ...[more]

PMID: 25551634

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N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.

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N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins.

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