430438-75-8Relevant academic research and scientific papers
Comparison of acyl-CoA synthetic activities and enantioselectivity toward 2-arylpropanoic acids in firefly luciferases
Kato, Dai-Ichiro,Yokoyama, Keisuke,Hiraishi, Yoshihiro,Takeo, Masahiro,Negoro, Seiji
experimental part, p. 1758 - 1762 (2012/02/02)
Measurement of thioesterification activities for dodecanoic acid (C12) and ketoprofen was done using five firefly luciferases, from Pyrocoelia miyako (PmL), Photinus pyralis (PpL), Luciola cruciata (LcL), Hotaria parvura (HpL), and Luciola mingrelica (LmL). Among these, PmL, PpL, and LcL showed the expected thioesterification activities toward both substrates. All the enzymes exhibited (R)-enantioselectivity toward ketoprofen, which had same tendency as firefly luciferase from Luciola lateralis (LUC-H). HpL and LmL, however, did not accept ketoprofen, although they had thioesterification activity toward C12. These results indicate that the substrate acceptance of luciferases for the thioesterification reaction varies dramatically relying on the origin of firefly. Hence we focused primarily on PmL and investigated the effect of pH on enzymatic activity. In addition, by determining the kinetic parameters at various pH values, we verified that the kcat parameter contributed to the preferential enantioselectivity of this enzyme.
Enantiodifferentiation of ketoprofen by Japanese firefly luciferase from Luciola lateralis
Kato, Dai-Ichiro,Tatsumi, Tomohiro,Bansho, Asami,Teruya, Keisuke,Yoshida, Hiromitsu,Takeo, Masahiro,Negoro, Seiji
experimental part, p. 140 - 146 (2012/01/19)
Recently, we found that firefly luciferase exhibited (R)-enantioselective thioesterification activity toward 2-arylpropanoic acids. In the case of Japanese firefly luciferase from Luciola lateralis (LUC-H), the E-value for ketoprofen was approximately 20. In this study, we used a spectrophotometric method to measure the catalytic activity of LUC-H. Using this method allowed us to judge the reaction efficiency easily. Our results confirmed that LUC-H exhibits enantioselective thioesterification activity toward a series of 2-arylpropanoic acids. The highest activity was observed with ketoprofen. We also observed high enzymatic activity of LUC-H toward long-chain fatty acids. These results were reasonable because LUC-H is homologous with long-chain acyl-CoA synthetase. To obtain further information about the enantiodifferentiation mechanism of the LUC-H catalyzed thioesterification of ketoprofen, we determined the kinetic parameters of the reaction relative to each of its three substrates: ketoprofen, ATP, and coenzyme A (CoASH). We found that whereas the affinities of each compound are not affected by the chirality of ketoprofen, enantiodifferentiation is achieved by a chirality-dependent difference in the kcat parameter.
Chiral inversion of 2-arylpropionyl-CoA esters by human α-methylacyl-CoA racemase 1A (P504S) - A potential mechanism for the anti-cancer effects of ibuprofen
Woodman, Timothy J.,Wood, Pauline J.,Thompson, Andrew S.,Hutchings, Thomas J.,Steel, Georgina R.,Jiao, Ping,Threadgill, Michael D.,Lloyd, Matthew D.
, p. 7332 - 7334 (2011/08/06)
Metabolic chiral inversion of 2-arylpropanoic acids (2-APAs; 'profens'), such as ibuprofen, is important for pharmacological activity. Several 2-APA-CoA esters were good racemisation substrates for human AMACR 1A, suggesting a common chiral inversion pathway for all 2-APAs and an additional mechanism for their anti-cancer properties.
