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Studies on deamidation mediated inactivation of cellular proteins and the role of protein isoaspartyl methyltransferase towards their repair

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Studies on deamidation mediated inactivation of cellular proteins and the role of protein isoaspartyl methyltransferase towards their repair
 
Creator Banerjee, Shakri
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description The spontaneous deamidation of asparaginyl residues at biological pH of 7.4 causes experimentally and biologically important changes resulting in the formation of inactive peptides and proteins [1]. In asparaginyl deamidation, the primary reaction products are aspartyl and isoaspartyl residues [1]. Deamidation at neutral pH introduces a negative charge at the deamidation site and sometimes also leads to β isomerization [2]. These alterations in structure affect the properties of peptides and proteins in chemically and biologically important pathways [1]. It has been suggested that isoaspartates in proteins serves as a molecular timer of biological events and as a mechanism for postsynthetic production of unique proteins of biological significance [3-5]. In the case of in vivo protein turnover, the use of deamidation as a molecular timer has been experimentally demonstrated [6-8]. Deamidation has been primarily observed to progressively increase in aging cells and tissues[9]. Cellular aging is a fundamental phenomenon that affects all somatic cells at definite points of time in their longevity cycle and whose manifestation varies within cell types. Aging in its essence encompasses all those processes that lead to a decline in the ability of the organism to cope with environmental stresses and is defined as the accumulation of diverse deleterious changes occurring in cells and tissues with time that are responsible for the increased risk of disease and death. The major theories of aging eg, the free radical theory [10], the immunologic theory[11], the inflammation theory[12], and mitochondrial theory [13] are all specific of a particular cause of aging, providing useful and important insights for the understanding of physiological changes occurring with aging. With progressive cellular aging, the vital biochemical process slows down and biologically relevant macromolecules accumulate undesirable modifications. Such modifications further impair cellular functions thus hastening the progression of aging.
 
Date 2015
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2508/1/TTHESIS_SHAKRI_BANERJEE.pdf
Banerjee, Shakri (2015) Studies on deamidation mediated inactivation of cellular proteins and the role of protein isoaspartyl methyltransferase towards their repair. PhD thesis, J U .
 
Relation http://www.eprints.iicb.res.in/2508/