title: Modulation of aldose reductase activity through S-thiolation by physiological thiols.
abstract: The glutathionyl-modified aldose reductase (GS-ALR2) is unique, among different S-thiolated enzyme forms, in that it displays a lower specific activity than the native enzyme (ALR2). Specific interactions of the bound glutathionyl moiety (GS) with the ALR2 active site, were predicted by a low perturbative molecular modelling approach. The outcoming GS allocation, involving interactions with residues relevant for catalysis and substrate allocation, explains the rationale behind the observed differences in the activity between GS-ALR2 and other thiol-modified enzyme forms. The reversible S-glutathionylation of ALR2 observed in cultured intact bovine lens undergoing an oxidative/non oxidative treatment cycle is discussed in terms of the potential of ALR2/GS-ALR2 inter-conversion as a response to oxidative stress conditions.
authors: Dipartimento di Fisiologia e Biochimica, Università di Pisa, Via S. Maria, 55, 56126, Pisa, Italy.
authors: M
authors: M
authors: Cappiello
authors: P
authors: P
authors: Amodeo
authors: B L
authors: BL
authors: Mendez
authors: A
authors: A
authors: Scaloni
authors: P G
authors: PG
authors: Vilardo
authors: I
authors: I
authors: Cecconi
authors: M
authors: M
authors: Dal Monte
authors: S
authors: S
authors: Banditelli
authors: F
authors: F
authors: Talamo
authors: V
authors: V
authors: Micheli
authors: F J
authors: FJ
authors: Giblin
authors: A
authors: A
authors: Del Corso
authors: U
authors: U
authors: Mura
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D007908:Lens, Crystalline / Q000201:enzymology; D008958:Models, Molecular; D018384:Oxidative Stress; D011487:Protein Conformation; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D000449:Aldehyde Reductase; D005978:Glutathione