title: Role of cysteine residues in the enhancement of chaperone function in methylglyoxal-modified human alpha A-crystallin.
abstract: We have previously demonstrated that the reaction of a physiological dicarbonyl, methylglyoxal (MGO) enhances the chaperone function of human alpha A-crystallin. MGO can react with cysteine, arginine, and lysine residues in proteins. Although the role of arginine and lysine residues in the enhancement of chaperone function has been investigated, the role of cysteine residues is yet to be determined. In this study, we have investigated the effect of MGO modification on the structure and chaperone function of alpha A-crystallin mutant proteins in which C131 and C142 were replaced either individually or simultaneously with isoleucine. MGO-modification resulted in improved chaperone function in all three alpha A-crystallin mutants, including the cysteine-free double mutant. The enhanced chaperone function was due to increased surface hydrophobicity and increased binding of client proteins. These results suggest that the two cysteine residues, even though they could be modified, do not take part in the MGO-induced improvement in the chaperone function of human alpha A-crystallin.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Pathology Building 311, 2085 Adelbert Road, Cleveland, OH 44106, USA.
authors.forename: Santosh R
authors.initials: SR
authors.lastname: Kanade
authors.forename: NagaRekha
authors.initials: N
authors.lastname: Pasupuleti
authors.forename: Ram H
authors.initials: RH
authors.lastname: Nagaraj
mesh_terms: D002942:Circular Dichroism; D003001:Cloning, Molecular; D003545:Cysteine / Q000235:genetics*; D006801:Humans; D011765:Pyruvaldehyde / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D038202:alpha-Crystallin A Chain / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins; D038202:alpha-Crystallin A Chain; D011765:Pyruvaldehyde; D003545:Cysteine