6ac2
Crystal Structure of HEWL at pH 2.2
Structural highlights
FunctionLYSC_CHICK Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1] Publication Abstract from PubMedNumerous efforts have been directed towards investigating the different stages leading to the fibrillation process in neurodegenerative diseases and finding the factors modulating it. In this study, using a wide range of molecular techniques as well as fibrillation kinetics coupled with differential scanning fluorimetry (DSF) and crystal structure determination of HEWL treated with cinnamaldehyde (Cin) and Phenyl ethyl alcohol (PEA) in their aroma form during fibrillation, we were able to identify the binding positions of Cin and PEA in HEWL. Additionally, crystal structures were used to suggest residues Thr43, Asn44, Arg45 and Arg68 as a plausible 'hotspot' promoting entrapment of intermediate species in the process of fibril formation in HEWL. We were also able to use DSF to show that Cin can significantly decrease the thermal stability of HEWL, promoting the formation of partially unfolded intermediate species. In conclusion, our data led us to emphasize that compounds in their 'aroma form' can influence the structure and stability of protein molecules and suggest reconsideration of HEWL as a model protein for fibrillation studies related to neurodegenerative diseases based on the initial structure of the proteins, whether globular (HEWL) or intrinsically disordered. Cinnamaldehyde and Phenyl Ethyl Alcohol promote the entrapment of intermediate species of HEWL, as revealed by structural, kinetics and thermal stability studies.,Seraj Z, Groves MR, Seyedarabi A Sci Rep. 2019 Dec 9;9(1):18615. doi: 10.1038/s41598-019-55082-1. PMID:31819148[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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