Large-Scale Domain Motions and Pyridoxal-5'-Phosphate Assisted Radical Catalysis in Coenzyme B12-Dependent Aminomutases

• Main Authors: Amarendra Nath Maity, Yung-Han Chen, Shyue-Chu Ke
• Format: Article
• Language: English
• Published: MDPI AG 2014-02-01
• Series: International Journal of Molecular Sciences
• Subjects: coenzyme B12 (5'-deoxyadenosylcobalamin; dAdoCbl); pyridoxal-5'-phosphate (PLP; vitamin B6); lysine 5,6-aminomutase; ornithine 4,5-aminomutase; isotope-edited electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) spectroscopy; density functional theory (DFT)
• Online Access: http://www.mdpi.com/1422-0067/15/2/3064

Lysine 5,6-aminomutase (5,6-LAM) and ornithine 4,5-aminomutase (4,5-OAM) are two of the rare enzymes that use assistance of two vitamins as cofactors. These enzymes employ radical generating capability of coenzyme B12 (5'-deoxyadenosylcobalamin, dAdoCbl) and ability of pyridoxal-5'-phosphate (PLP, vitamin B6) to stabilize high-energy intermediates for performing challenging 1,2-amino rearrangements between adjacent carbons. A large-scale domain movement is required for interconversion between the catalytically inactive open form and the catalytically active closed form. In spite of all the similarities, these enzymes differ in substrate specificities. 4,5-OAM is highly specific for D-ornithine as a substrate while 5,6-LAM can accept D-lysine and L-β-lysine. This review focuses on recent computational, spectroscopic and structural studies of these enzymes and their implications on the related enzymes. Additionally, we also discuss the potential biosynthetic application of 5,6-LAM.