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Structural Basis for Radical Reaction Mechanisms in the Actions of Lysine Aminomutases
Author(s) -
Frey Perry Allen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a43-d
Subject(s) - chemistry , isomerization , homolysis , lysine , adenosylcobalamin , bond cleavage , stereochemistry , aldimine , reaction intermediate , photochemistry , radical , catalysis , cofactor , organic chemistry , enzyme , biochemistry , amino acid
Lysine 2,3‐aminomutase (2,3‐LAM) catalyzes the isomerization of lysine to β‐lysine, and lysine 5,6‐aminomutase (5,6‐LAM) catalyzes the isomerization of β‐lysine to 3,5‐diaminohexane. Both reactions proceed by analogous radical mechanisms initiated by the 5′‐deoxyadenosyl radical (AdoCH 2 ·). The 5′‐deoxyadenosyl radical arises from S ‐adenosylmethionine in the reaction of 2,3‐LAM and from adenosylcobalamin in the reaction of 5,6‐LAM. Both enzymes require pyridoxal‐5′‐phosphate (PLP) to facilitate radical isomerization. Homolytic scission of the Co–C5′ bond in adenosylcobalamin reversibly generates AdoCH 2 · in 5,6‐LAM, and reductive cleavage of the S–C5′ bond in S‐adenosylmethionine reversibly generates AdoCH 2 · in 2,3‐LAM. The structure of 5,6‐LAM is composed of TIM barrel and Rossmann fold subunits. Cob(III)alamin and PLP are bound at the interface. The radical intermediates of 2,3‐LAM are known by EPR, and the mechanism of reductive cleavage of S ‐adenosylmethionine is known by XAFS and ENDOR spectroscopies. The structure of 2,3‐LAM shows a β‐crescent enclosing the active site, which binds the essential [4Fe–4S] cluster, to which S ‐adenosylmethionine is ligated, in close proximity to the aldimine complex of PLP and lysine.