D-ornithine 4,5-aminomutase (OAM)

D-ornithine 4,5-aminomutase (OAM) is a specialized bacterial enzyme responsible for the anaerobic fermentation of amino acids in various microorganisms, including the human pathogen Clostridioides difficile [UniProt, PMID: 28325765]. It catalyzes the reversible intramolecular migration of the delta-amino group of D-ornithine to the C4 position, producing (2R,4S)-2,4-diaminopentanoate [PMID: 18997010, 21899873]. This complex transformation involves a radical-based mechanism that requires two essential cofactors: adenosylcobalamin (coenzyme B12), which generates the initiating 5'-deoxyadenosyl radical, and pyridoxal 5'-phosphate (PLP), which stabilizes the substrate as a Schiff base [PMID: 18997010, 21899873]. Structurally, the enzyme typically exists as a heterotetramer composed of alpha and beta subunits, often designated as OraS and OraE [UniProt, PMID: 18997010]. Because OAM is vital for the metabolic fitness of anaerobic pathogens and is absent in humans, it is viewed as a potential target for the development of selective anti-infective agents [PMID: 28325765]. Experimental inhibitors like 2,4-diaminobutyric acid (DAB) disrupt the catalytic cycle by forming stable radical intermediates that prevent enzyme turnover [PMID: 21899873].

Other names

Ornithine 4,5-aminomutaseD-ornithine aminomutaseD-ornithine 5,4-aminomutaseORAOraEOraS

Radical-mediated 1,2-migration of the delta-amino group of D-ornithine to the C4 position using adenosylcobalamin and pyridoxal phosphate cofactors; suicide inhibition occurs through the formation of overstabilized radical intermediates.