title: Chemometric study of the aggregation of alcohol dehydrogenase and its suppression by beta-caseins: a mechanistic perspective.
abstract: Molecular chaperones interact preferentially with certain aggregation-prone intermediates of target protein molecules. An estimation of the chaperone activity based on suppression of aggregation is required to be mechanistically understood. In this study, the multivariate curve resolution chemometric technique was applied on horse alcohol dehydrogenase (ADH) UV-spectra under thermal stress, to obtain the required information about the number and change in concentrations of the species involved. Chemometric analysis of UV-absorption spectra of horse ADH under thermal stress, led to the existence of three different molecular species including native (N), aggregation-prone intermediate (I) and final aggregate (A) species. Appearance and buildup of two molecular species I and A were connected to the disappearance of N-species. In the presence of beta-caseins (BCN), however, a new complex between I and BCN (I-BCN) was formed. Meanwhile, by accretion of concentration of I-BCN complex, the light scattering intensity diminished. The data presented in this study clearly demonstrate that the interaction of BCN as a chaperone molecule with I-species takes place in a temperature-dependent manner and leads to a reversible I-BCN complex. In the absence of chaperones, I-state is subsequently converted to the final aggregate species. In the presence of BCN, this molecular species could be converted to the final aggregate state and/or form the I-BCN complex.
authors: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors: Mostafa
authors: M
authors: Hassanisadi
authors: Abolfazl
authors: A
authors: Barzegar
authors: Reza
authors: R
authors: Yousefi
authors: Michèle
authors: M
authors: Dalgalarrondo
authors: Jean-Marc
authors: JM
authors: Chobert
authors: Thomas
authors: T
authors: Haertlé
authors: Ali Akbar
authors: AA
authors: Saboury
authors: Ali Akbar
authors: AA
authors: Moosavi-Movahedi
mesh_terms: D000042:Absorption; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002162:Camelus / Q000378:metabolism; D002364:Caseins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D006736:Horses; D006801:Humans; D016018:Least-Squares Analysis; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D002364:Caseins; D018832:Molecular Chaperones; D000426:Alcohol Dehydrogenase