NDLI: S-linked protein homocysteinylation: identifying targets based on structural, physicochemical and protein–protein interactions of homocysteinylated proteins

Content Provider	Springer Nature Link
Author	Silla, Yumnam Sundaramoorthy, Elayanambi Talwar, Puneet Sengupta, Shantanu
Copyright Year	2013
Abstract	An elevated level of homocysteine, a thiol-containing amino acid is associated with a wide spectrum of disease conditions. A majority (>80 %) of the circulating homocysteine exist in protein-bound form. Homocysteine can bind to free cysteine residues in the protein or could cleave accessible cysteine disulfide bonds via thiol disulfide exchange reaction. Binding of homocysteine to proteins could potentially alter the structure and/or function of the protein. To date only 21 proteins have been experimentally shown to bind homocysteine. In this study we attempted to identify other proteins that could potentially bind to homocysteine based on the criteria that such proteins will have significant 3D structural homology with the proteins that have been experimentally validated and have solvent accessible cysteine residues either with high dihedral strain energy (for cysteine–cysteine disulfide bonds) or low pKa (for free cysteine residues). This analysis led us to the identification of 78 such proteins of which 68 proteins had 154 solvent accessible disulfide cysteine pairs with high dihedral strain energy and 10 proteins had free cysteine residues with low pKa that could potentially bind to homocysteine. Further, protein–protein interaction network was built to identify the interacting partners of these putative homocysteine binding proteins. We found that the 21 experimentally validated proteins had 174 interacting partners while the 78 proteins identified in our analysis had 445 first interacting partners. These proteins are mainly involved in biological activities such as complement and coagulation pathway, focal adhesion, ECM-receptor, ErbB signalling and cancer pathways, etc. paralleling the disease-specific attributes associated with hyperhomocysteinemia.
Starting Page	1307
Ending Page	1316
Page Count	10
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	44
Issue Number	5
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2013-02-12
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Homocysteine Homologous structure Disulfide Dihedral strain energy pKa Protein–protein interaction Biochemistry Analytical Chemistry Biochemical Engineering Life Sciences Proteomics Neurobiology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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