title: Induction of amyloidogenicity in wild type HEWL by a dialdehyde: analysis involving multi dimensional approach.
abstract: Physiological conditions corresponding to oxidative stress deplete the level of enzyme glyoxalase, facilitating a hike in the serum concentration of glyoxal. Simulating an elevated in vivo level of glyoxal, we tested (50%, v/v) concentration of glyoxal to interact with HEWL. Initially, docking study revealed that glyoxal binds in the hydrophobic core of the enzyme. The interaction between the dialdehyde (glyoxal) and the enzyme (HEWL) followed a three step transition involving pre-molten and molten globule states formed on days 7 and 15 of incubation respectively, which were characterised by an increase in the ANS fluorescence intensity compared to the native state. These molten globule states upon further incubation on day 20 resulted in the formation of aggregates which were characterised by an increase in ThT fluorescence intensity, red shift in Congo red absorbance, negative ellipticity peak at 217 nm in the far-UV CD and the loss of signals at 284, 290 and 294 nm in the near-UV CD spectra. Finally, TEM confirmed the authenticity of lysozyme fibril formation by displaying rod like fibrillar structure.
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Naveed Ahmad
authors.initials: NA
authors.lastname: Fazili
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Waseem Feeroze
authors.initials: WF
authors.lastname: Bhat
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202002, India. Electronic address: aabgeenanaim@gmail.com.
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
mesh_terms: D000818:Animals; D001665:Binding Sites; D004789:Enzyme Activation; D006037:Glyoxal / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012984:Software; D064878:Web Browser
chemical_list: D008024:Ligands; D006037:Glyoxal; D009113:Muramidase
keywords: Absorbance; Aggregation; Docking; Ellipticity; Fibrils; β-Sheet