Pre-Steady-State Kinetic and Structural Analysis of Interaction of Methionine {gamma}-Lyase from Citrobacter freundii with Inhibitors [Enzymology]

November 14th, 2014 by Kuznetsov, N. A., Faleev, N. G., Kuznetsova, A. A., Morozova, E. A., Revtovich, S. V., Anufrieva, N. V., Nikulin, A. D., Fedorova, O. S., Demidkina, T. V.

MGL catalyzes the γ-elimination of L-methionine and its derivatives as well as the β-elimination of L-cysteine and its analogs. These reactions yield α-keto acids and thiols. The mechanism of chemical conversion of amino acids includes numerous reaction intermediates. The detailed analysis of MGL interaction with glycine, L-alanine, L-norvaline and L-cycloserine was performed by pre-steady-state stopped-flow kinetics. The structure of side chains of the amino acids is important both for their binding with enzyme and for the stability of the external aldimine and ketimine intermediates. X-ray structure of MGL-L-cycloserine complex has been solved at 1.6 Å resolution. The structure models ketimine intermediate of physiological reaction. The results elucidate the mechanisms of the intermediates interconversion at the stages of external aldimine and ketimine formation.
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