Investigations of the kinetic and chemical mechanisms of tryptophan 2-monooxygenase /

Bibliographic Details
Main Author: Emanuele, John J.
Other Authors: Pace, C.N (degree committee member.), Raushel, Frank M. (degree committee member.), Park, William (degree committee member.)
Format: Thesis Book
Language:English
Published: 1994.
Subjects:
Online Access:Link to OAKTrust copy
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Description
Abstract:The flavoprotein tryptophan 2-monooxygenase (TMO) from the plant pathogen Pseudomonas syringae pv. savastanoi catalyzes the oxidative decarboxylation of tryptophan to indole-3-acetamide, carbon dioxide and water. TMO is involved in the bacterial production of auxin. The enzyme was overexpressed in and purified to homogeneity from E coli. Steady state and rapid reaction kinetic methods were used to study the reaction with L-tryptophan at pH 8.3 and 25 °C. The reduction of TMO by L-tryptophan was consistent with equilibrium binding of substrate followed by two reversible steps. The first step was isotope sensitive with a rate constant of 115 s e c 1, while the second had a rate constant of 2.5 s e c 1. Indole-pyruvate was formed with a rate constant of 107 sec*1, consistent with all of the chemistry occurring during the isotope sensitive step. Oxygen reacted with the reduced enzyme oxidized substrate complex with a rate constant of 195 mM*1 sec*1. The rate constant for product release was calculated to be 14.9 sec*1. The substrate's amino group and a group on the enzyme with a pKa of 6.0 had to be protonated; deprotonation of a group on the enzyme with a pKa of 10 increased activity. Deprotonation of a group with a pKa of 8.5 resulted in an increase in V/K02(met) value but had no effect on V/K02(trp) ° r V/K02(phe)- Deprotonation of a group on the enzyme increased Vmax; the pKa of this group was 6.3 with L-methionine, 7.7 with L-phenylalanine and 8.5 with Ltryptophan. DV/K(trp) values were small, consistent with a high forward commitment. At high or low pH the °V/Kmet value was 5.2. The °V/Kala value at pH 8.3 was 5.3. The P°V/Kala value was 0.96±0.04; this is inconsistent with a hydride transfer mechanism. DVmax values with Ltryptophan and L-phenylalanine at pH 8.3 were small, consistent with product release being rate limiting.
Item Description:Vita.
"Major subject: Biochemistry."
In title, there are numerals.
Physical Description:xv, 130 leaves : illustrations ; 28 cm
Bibliography:Includes bibliographical references.