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Discovery and Physiological Role

Lysine and ornithine are degraded in a similar manner in Clostridium sticklandii, a Gram-positive anaerobe. 5,6-LAM participates in the second step of the fermentation pathway of lysine in which lysine is converted to acetic acid, ammonia and butyric acid, while 4,5-OAM takes part in the first step of the fermentation pathway of ornithine, in which ornithine is converted to acetate, carbon dioxide, alanine and ammonia by clostridia []. Dr. Theressa Stadtman and coworkers first discovered and performed initial studies on 5,6-LAM [,]. Initially, it was assumed that there are two distinct enzymes [–] displaying 5,6-aminomuatase activity relating to two distinct substrates, d-lysine and l-β-lysine. Later, it was found that these are the same enzyme, which can accept two different substrates [,]. Dyer and Costilow [] reported OAM activity for the first time in crude extracts, and a subsequent study by Tsuda and Friedmann on cofactor requirements was performed using partially purified extracts []. Later, separation, purification and properties of 4,5-OAM was reported by Somack and Costilow [].

Pyridoxal-5′-Phosphate (PLP) Binding Site and Active Site Residues

d-Ornithine soaked 4,5-OAM crystals [] provided the glimpse of substrate bound structure, in which Lys629 has moved away from PLP and ornithine is bound to PLP through external aldimine. Hydrogen bonding and salt bridge interactions of Gln299, Arg297, His225, Tyr160, and His182 with carboxylate moiety of d-ornithine and electrostatic interaction between Glu81 and α-amine anchor the substrate in the active site (). The hydrogen bonding interaction of pyridine nitrogen with Ser162 is absent. Similar interactions are observed in the case of substrate analog dl-2,4-diaminobutyric acid (2,4-DAB) with few exceptions. His225 and Tyr160 do not make hydrogen bonds with the carboxylate while Ser162 and Lys629 make additional hydrogen bonds with pyridine nitrogen and phenolic oxygen, respectively ().