Chemical modification of an arginine residue in aldose reductase is enhanced by coenzyme binding: further evidence for conformational change during the reaction mechanism.
Chemical modification of pig muscle aldose reductase (ALR2) with the arginine specific reagent phenylglyoxal resulted in the inactivation of the enzyme. This inactivation exhibited pseudo-first order kinetics typical of active-site directed chemical modification. Inactivation of ALR2 by [7-C14] phenylglyoxal in the absence of NADPH or NADP+ followed by tryptic digestion resulted in the isolation by HPLC of one major and one minor radioactive peptide. Protein sequencing revealed that the major peptide contained a modified arg268, a residue located in the coenzyme binding site. The minor radioactive peptide and the single radioactive peptide isolated from ALR2 inactivated in the presence of NADP+ contained chemically modified arg293. The arginine residue modified at the active site is positioned to bind the 2'-OH phosphate group of the ribose sugar of the adenine moiety of NADP+. Arg293 is present on the C-terminal loop of ALR2. The enhancement of Arg293 modification by phenylglyoxal in the presence of NADP+ indicates that this C-terminal loop may be involved in the slow conformational change that occurs during the reaction sequence upon coenzyme binding.[1]References
- Chemical modification of an arginine residue in aldose reductase is enhanced by coenzyme binding: further evidence for conformational change during the reaction mechanism. Flynn, T.G., Kubiseski, T.J. Adv. Enzyme Regul. (1993) [Pubmed]
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