InterPro domain: IPR004313

The two acireductone dioxygenase enzymes (ARD and ARD', previously known as E-2 and E-2') from Klebsiella pneumoniae share the same amino acid sequence Q9ZFE7 , but bind different metal ions: ARD binds Ni2+, ARD' binds Fe2+ [ 1 ]. ARD and ARD' can be experimentally interconverted by removal of the bound metal ion and reconstitution with the appropriate metal ion. The two enzymes share the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, but yield different products. ARD' yields the alpha-keto precursor of methionine (and formate), thus forming part of the ubiquitous methionine salvage pathway that converts 5'-methylthioadenosine (MTA) to methionine. This pathway is responsible for the tight control of the concentration of MTA, which is a powerful inhibitor of polyamine biosynthesis and transmethylation reactions [ 2 ]. ARD yields methylthiopropanoate, carbon monoxide and formate, and thus prevents the conversion of MTA to methionine. The role of the ARD catalysed reaction is unclear: methylthiopropanoate is cytotoxic, and carbon monoxide can activate guanylyl cyclase, leading to increased intracellular cGMP levels [ 3 , 3 ].

Eukaryotic aci-reductone dioxygenase (ARD), also known as 1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase, acts in the methionine salvage pathway [ 3 ]. Several homologous ARD genes have been identified in plants [ 4 ].

1. One protein, two enzymes. J. Biol. Chem. 274, 1193-5
2. Mechanistic studies of two dioxygenases in the methionine salvage pathway of Klebsiella pneumoniae. Biochemistry 40, 6379-87
3. Membrane-type 1 matrix metalloproteinase cytoplasmic tail binding protein-1 (MTCBP-1) acts as an eukaryotic aci-reductone dioxygenase (ARD) in the methionine salvage pathway. Genes Cells 10, 565-74
4. The immediate-early ethylene response gene OsARD1 encodes an acireductone dioxygenase involved in recycling of the ethylene precursor S-adenosylmethionine. Plant J. 44, 718-29