4-Oxalocrotonate tautomerase

Poelarends GJ, R Saunier, DB Janssen (2001) fra 5-3-chloroacrylic acid dehalogenase from Pseudomonas pavonaceae 170 shares structural and mechanistic similarities with 4-oxalocrotonate tautomerase. J Bacteriol 183 4269-4277. 

Keywords QM/MM, 4-oxalocrotonate tautomerase, Free energy Perturbation, Enzyme catalysis... 

Cisneros GA, Liu H, Zhang Y, Yang W (2003) Ab initio QM/MM study shows there is no general acid in the reaction catalyzed by 4-oxalocrotonate tautomerase. J Am Chem Soc 125 10384—10393... 

Cisneros GA, Wang M, Silinski P, Fitzgerald MC, Yang WT (2004) The protein backbone makes important contributions to 4-oxalocrotonate tautomerase enzyme catalysis understanding from theory and experiment. Biochemistry 43 6885-6892... 

Metanis N, Brik A, Dawson PE, Keinan E (2004) Electrostatic interactions dominate the catalytic contribution of arg39 in 4-oxalocrotonate tautomerase. J Am Chem Soc 126 12726-12727... 

Oxalocrotonate tautomerase. This bacterial enzyme, which functions in the degradation of toluene (Chapter 25), is actually an isomerase. It catalyzes rapid interconversion of an unconjugated unsaturated a-oxoacid such as 4-oxalocrotonate with an intermediate enol (which may leave the enzyme) and the isomeric conjugated oxoacid (Eq. 13-31).168-170 A related 5-carboxymethyl-2-hydroxymuconate isomerase... 

The pKa of 6.2 has been associated with the amino-terminal proline l.172 4-Oxalocrotonate tautomerase is one of a small group of enzymes that have been synthesized nonenzymatically with both l amino acids and as a mirror image constructed with d amino acids.173... 

The backbone dynamics of 4-oxalocrotonate tautomerase, a 41-kDa homo-hexamer with 62 residues per subunit, and its complex with a substrate analogue have been analyzed by the model-free formalism.60 Binding of the analogue freezes the motion of some of the backbone NH vectors in the active site, leading to a loss of entropy (Chapter 2). 

Stivers, J. T., Abeygunawardana, C., Mildvan, A. S. 1996. 15N NMR relaxation studies of free and inhibitor-bound 4-oxalocrotonate tautomerase Backbone dynamics and entropy changes of an enzyme upon inhibitor binding. Biochemistry 35, 16036-16047. 

N NMR Relaxation Studies of Free and Inhibitor-Bound 4-Oxalocrotonate Tautomerase Backbone Dynamics and Entropy Changes of an Enzyme upon Inhibitor Binding. 

Zandvoort, E., Baas, B.-J., Quax, W. J., and Poelarends, G. J., Systematic screening for catalytic promiscuity in 4-oxalocrotonate tautomerase Enamine formation and aldolase activity. ChemBioChem 2011,12 (4), 602-609. 

Geertsema, E. M., Miao, Y, Tepper, P. G., de Haan, R, Zandvoort, E., and Poelarends, G. J., Biocatalytic michael-type additions of acetaldehyde to nitroolefins with the proline-based enzyme 4-oxalocrotonate tautomerase yielding enantioenriched y-nitroaldehydes. Chem. Eur. J. 2013,19 (43), 14407-14410. 

Bridging the gap between organocatalysis and biocatalysis has been attained with the promiscuous enzyme 4-oxalocrotonate tautomerase (4-OT) that has been shown to catalyse the Michael-type addition of acetaldehyde to nitrostyrene. The reaction proceeds in water, affords the (5)-configured product in 89% ee, and is believed to proceed via enamine formation that employs the amino-terminal proline of the enzyme. 2 0... 

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