title: In search of radical intermediates in the reactions catalyzed by lysine 2,3-aminomutase and lysine 5,6-aminomutase.
abstract: High-level ab initio calculations have been used to study radical intermediates in the reactions catalyzed by lysine 2,3-aminomutase (2,3-LAM) and lysine 5,6-aminomutase (5,6-LAM). The reactions of these enzymes with the substrate analogues 4-oxalysine (4-OL), 4-thialysine (4-TL), or trans-4,5-dehydrolysine (t-4,5-DL) are rationalized in terms of stabilization provided by the substituent to the adjacent radical center. Large changes in the exothermicity accompanying the initial H-abstraction are observed relative to the lysine reference values that follow the series 4-OL < 4-TL < t-4,5-DL. These changes have the primary effect of increasing the endothermicity for subsequent ring-closure to form the putative aziridinylcarbinyl radical intermediate. Such stabilization is consistent with experimental observations of the substrate-derived radical (S*) in the reaction of 2,3-LAM with 4-TL as well as the ability of t-4,5-DL to act as an irreversible inhibitor of 2,3-LAM. Our calculations suggest that 4-TL and trans-3,4-dehydrolysine may also permit experimental characterization of S* radicals in the reactions catalyzed by 5,6-LAM. Strategies for modifying PLP are presented that might lead to the first observation of the aziridinylcarbinyl radical intermediate (I*) in the aminomutase-catalyzed reactions.
authors.affiliation: School of Chemistry and ARC Centre of Excellence in Free Radical Chemistry and Biotechnology, University of Sydney, Sydney, NSW 2006, Australia. sandala@chem.usyd.edu.au
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sandala
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.forename: Leo
authors.initials: L
authors.lastname: Radom
mesh_terms: D002384:Catalysis; D005609:Free Radicals / Q000737:chemistry; D019751:Intramolecular Transferases / Q000378:metabolism*; D008239:Lysine; D015394:Molecular Structure; D013379:Substrate Specificity
chemical_list: D005609:Free Radicals; D019751:Intramolecular Transferases; C021518:lysine 2,3-aminomutase; C403167:D-lysine 5,6-aminomutase; D008239:Lysine