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

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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/