<p>.<br></p><p>The self-assembly of single amino acids is very important topic of
research since there are plethora of diseases like phenylketonuria,
tyrosinemia, hypertryptophanemia, hyperglycinemia, cystinuria and maple syrup
urine disease to name a few which are caused by the accumulation or excess of
amino acids. These are in-born errors of metabolisms (IEM’s) which are caused
due to the deficiency of enzymes involved in catabolic pathways of these
enzymes. Hence, it is very pertinent to understand the fate of these excess
amino acids in the body and their self-assembling behaviour at molecular level.
From the previous literature reports it may be surmised that the single amino
acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine assemble
to amyloid like structures, and hence have important implications in the pathophysiology
of IEM’s like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and
hypermethioninemia respectively. In this manuscript we report the self-assembly
of lysine hydrocholride to fiber like structures in deionized water. It could
be observed that lysine assemble to globular structures in fresh condition and
then gradually changes to fiber like morphologies by self-association over time
after 24 hours. These fibers gradually change to tubular morphologies after 3
day followed by fractal irregular morphologies in 10 and 15 days respectively. Notably,
lysine exists as positively charged amino acid at physiological pH and the
amine groups in lysine remain protonated. Hence, the self-assembling properties
of lysine hydrochloride in deionized water is also pertinent and give insights
into the fate of this amino acid in body in case it remains unmetabolized.
Further, MTT assays were done to analyse the toxicities of these aggregates and
the assay suggest their cytotoxic nature on SHSY5Y neural cell lines. Hence, the
aggregation of lysine may be attributed to the pathological symptoms caused in
diseases like hyperlysinemia which is associated with the neurological problems
like seizures and short-term memory as observed in case of amyloid diseases
like Parkinson’s and Alzheimer’s to name a few.</p>
Mutagenesis studies to determine the key interfacial amino acid residues that govern the self-assembly of the ferritin protein cages