On the interpretation of quantitative structure-function activity relationship data for lactate oxidase

Proceedings of the National Academy of Sciences of the United States of America
K YoritaV Massey

Abstract

The native flavin, FMN, has been removed from the l-lactate oxidase of Aerococcus viridans, and the apoprotein reconstituted with 12 FMN derivatives with various substituents at the flavin 6- and 8-positions. Impressive linear relationships are exhibited between the sum of the Hammett final sigma(para) and final sigma(ortho) parameters and the redox potentials of the free flavins, and between the redox potentials of the free and enzyme-bound flavins. Rapid reaction kinetics studies of the reconstituted enzymes with the substrates l-lactate and l-mandelate show an increase in the reduction rate constant with increasing redox potential, except that, with lactate, a limiting rate constant of approximately 700 s(-1) is obtained with flavins of high potential. Similar breakpoints are found in plots of the rate constants for flavin N5-sulfite adduct formation and for the reaction of the reduced enzymes with molecular oxygen. These results are interpreted in terms of a two-step equilibrium preceding the chemical reaction step, in which the second equilibrium step provides an upper limit to the rate with which the particular substrate or ligand is positioned with the flavin in the correct fashion for the observed chemical reaction to o...Continue Reading

References

Sep 7, 2007·Applied Microbiology and Biotechnology·Cuiqing MaPing Xu
Jan 16, 2003·Biochimica Et Biophysica Acta·Marco H HeftiWillem J H Van Berkel
Oct 31, 2001·European Journal of Biochemistry·C M HarrisSandro Ghisla
Nov 19, 2003·European Journal of Biochemistry·Marco H HeftiWillem J H Van Berkel
Dec 22, 2011·The Journal of Biological Chemistry·He G SunHung-Wen Liu
Mar 10, 2009·Applied and Environmental Microbiology·Roslina A NawawiAndrew C Barnes
Jul 10, 2013·Journal of Bacteriology·Simone LangerMatthias Mack
Nov 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·K YoritaV Massey
Sep 26, 2003·Journal of Enzyme Inhibition and Medicinal Chemistry·Sergio A StreitenbergerFrancisco García-Carmona
Apr 8, 2006·Trends in Biochemical Sciences·Andrea Mattevi
Sep 18, 2012·Biochimica Et Biophysica Acta·Isaias LansMilagros Medina
May 22, 2002·The Journal of Biological Chemistry·Silvia SacchiLoredano Pollegioni
Jan 18, 2007·Journal of Computational Chemistry·Yoong-Kee ChoeKichisuke Nishimoto
Jul 11, 2002·The Journal of Biological Chemistry·Nora TahallahAlbert J R Heck
Apr 12, 2016·Angewandte Chemie·Julia SchwarzMatthias Mack
Jul 22, 2006·The Biochemical Journal·Louis LimAlice Vrielink

Citations

Sep 1, 1991·Archives of Biochemistry and Biophysics·X L Shi, N S Dalal
Apr 20, 1990·Journal of Molecular Biology·Z X Xia, F S Mathews
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·Z X XiaF S Mathews
Jun 1, 1980·Biochemical Society Transactions·V Massey, P Hemmerich
May 1, 1993·European Journal of Biochemistry·P MacherouxY Lindqvist
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·Andrea MatteviB Curti
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·K YoritaV Massey
Apr 1, 1976·Applied Optics·R Olshansky, D A Nolan

Related Concepts

L-lactate
Snake Venoms
Apoenzymes
Derivatives
Lactate
Enzymes, antithrombotic
Structure-Activity Relationship
Adduct
Plasma Protein Binding Capacity
Lactic Acid Measurement

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