Studies of the inhibition of aldose reductase: evidence for multiple site binding.
1. Comparison of structure-inhibition relationships and kinetic data between the N-[(4-benzoylamino)phenyl]sulfonyl]amino acids (BAPS-amino acids) and phenylsulfonylamino acids (PS-amino acids) suggests that the additional benzoyl moiety present in the BAPS-amino acids enhances inhibition by direct interaction with aldose reductase (EC 1.1.1.21) without altering the mode of interaction with the enzyme. 2. Also the 2-, 3- and 4-nitro regioisomers of BAPS-glycine (NBAPSG) display parallel structure- inhibition relationships with the 2-, 3- and 4-nitrobenzaldehyde substrates and the 2-, 3- and 4-nitroacetophenone competitive inhibitors. 3. Competition studies and multiple inhibition analyses demonstrate that the 4-nitrobenzoyl group of 4-NBAPSG binds at the substrate site of aldose reductase, while the PS-glycine moiety of 4-NBAPSG binds cooperatively at a distinct site.
Mayfield
C A
CA
School of Pharmacy, Auburn University, Alabama.
DeRuiter
J
J
D000449:Aldehyde Reductase / Q000032:analysis* / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D007908:Lens, Crystalline / Q000201:enzymology*; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000032:analysis*; D013450:Sulfones / Q000494:pharmacology*
D000596:Amino Acids; D013450:Sulfones; C062604:N-(((4-benzoylamino)phenyl)sulfonyl)glycine; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D005998:Glycine