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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Frey, Perry A. Ruzicka, Frank J. |
| Description | Author Affiliation: Ruzicka FJ ( Department of Biochemistry, University of Wisconsin-Madison, 1710 University Avenue, Madison, Wisconsin 53726, USA.) |
| Abstract | Lysine 2,3-aminomutase (LAM) catalyzes the interconversion of L-lysine and L-ß-lysine, a component of a number of antibiotics. The reaction requires the cofactors S-adenosyl-L-methionine (SAM), pyridoxal-5'-phosphate (PLP), and a [4Fe-4S] cluster. LAM is a founding member of the radical SAM superfamily of enzymes. LAM is highly specific for L-lysine and will not accept most other amino acids as substrates. L-alanine and L-2-aminobutyrate at 0.2 M react as substrates for LAM at, respectively, 5 × 10(-6) and 8 × 10(-5) times the rate with saturating L-lysine. Saturating ethylamine accelerates the L-alanine reaction 70-fold, and saturating methylamine accelerates the L-2-aminobutyrate reaction 47-fold. The primary amines binding at the active site of LAM with L-alanine or L-2-aminobutyrate simulate L-lysine. The steady-state kinetics of the reaction of L-alanine + ethylamine displays negative cooperativity with respect to L-alanine. The second-order rate constant for production of ß-alanine in the reaction of L-alanine and saturating ethylamine is 0.040 M(-1) s(-1), which is 2 × 10(-5) times the value of k(cat)/K(m) for the reaction of L-lysine. When L-lysine is at a concentration 1/16th of K(m), the lysyl-free radical intermediate is hardly detectable by EPR; however, the addition of L-alanine at high concentration (0.2 M) enhances free radical formation, and the addition of ethylamine further enhances radical formation. These facts complement the kinetic observations and support negative cooperativity in the reaction of L-alanine as a substrate for LAM. Present results and independent evidence support negative cooperativity in the reaction of L-lysine as well. |
| ISSN | 15206106 |
| e-ISSN | 15205207 |
| Journal | The Journal of Physical Chemistry B |
| Issue Number | 49 |
| Volume Number | 114 |
| Language | English |
| Publisher | American Chemical Society (United States) |
| Publisher Date | 2010-12-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Intramolecular Transferases Chemistry Catalytic Domain Kinetics Molecular Structure Beta-Alanine Metabolism Research Support, N.I.H., Extramural Physical chemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Surfaces, Coatings and Films Materials Chemistry Medicine Physical and Theoretical Chemistry |
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