The inhibitory effect of various indolyl amino acid derivatives on arginase activity in macrophages.
Numerous indolyl amino acids and their derivatives inhibited arginase activity. The inhibition was found to be non-competitive, - at least partly - allosteric, and independent on manganese ions in the active site, and it cannot be explained by the dissociation of arginase homotrimers. Indole alone is weakly inhibitory; however, the presence of three-carbon side chains and their net charges is favorable for the inhibition. The binding of the inhibitory compounds caused only minor changes in the steric structure of arginase: a slight increase in alpha-helix content was detected by circular dichroism together with a decrease in parallel pleated sheet and beta-turn sections. A slight alteration in the tertiary structure was also found using tryptophane fluorescence studies, but buried apolar side chains were not transposed to the protein surface. Computer studies that were performed did not provide additional structural information.
Hrabák
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A
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University Medical School, Budapest, Hungary. hrabak@puskin.sote.hu
Bajor
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T
Mészáros
G
G
D000596:Amino Acids / Q000494:pharmacology*; D024322:Amino Acids, Aromatic / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors*; D002417:Cattle; D002942:Circular Dichroism; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D021122:Protein Subunits / Q000737:chemistry; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D024322:Amino Acids, Aromatic; D007211:Indoles; D021122:Protein Subunits; D008345:Manganese; D001119:Arginase