Protein Family Models

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 Swiss:Q9ZFE7, but bind different metal ions: ARD binds Ni2+, ARD' binds Fe2+. 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 [1,2]. 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 [1,2]. This family also contains other members, whose functions are not well characterised. [1]. 11371200. Mechanistic Studies of Two Dioxygenases in the Methionine Salvage Pathway of Klebsiella pneumoniae(,). Dai Y, Pochapsky TC, Abeles RH;. Biochemistry 2001;40:6379-6387. [2]. 9880484. One protein, two enzymes. Dai Y, Wensink PC, Abeles RH;. J Biol Chem 1999;274:1193-1195. (from Pfam)

Date:

2024-10-16

1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase, also called acireductone dioxygenase, catalyzes the oxidation of 1,2-dihydroxy-3-keto-5-methylthiopentene to yield two different products depending on which active site metal is present (Fe2+ or Ni2+) as part of the methionine salvage pathway

Date:

2024-09-24