InterPro domain: IPR033890

This subgroup of NDP-sugar epimerase/dehydratases are extended short-chain dehydrogenase/reductases (SDRs); they have the characteristic active site tetrad, and an NAD-binding motif: TGXXGXX[AG], which is a close match to the canonical NAD-binding motif. Members include Arabidopsis thaliana GDP-mannose-3',5'-epimerase which catalyzes the epimerization of GDP-alpha-D-mannose to form GDP-beta-L-galactose [ 1 ]. It also catalyses an epimerization reaction that releases GDP-L-gulose, an intermediate that could be dedicated for the de novo biosynthesis of vitamin C in plants [ 2 ].

Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids [ 3 , 4 , 5 , 6 ].

1. Structure and function of GDP-mannose-3',5'-epimerase: an enzyme which performs three chemical reactions at the same active site. J. Am. Chem. Soc. 127, 18309-20
2. GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate for the de novo biosynthesis of vitamin C in plants. J. Biol. Chem. 278, 47483-90
3. Short-chain dehydrogenases/reductases (SDR). Biochemistry 34, 6003-13
4. Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell. Mol. Life Sci. 65, 3895-906
5. Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem. Biol. Interact. 143-144, 247-53
6. Coenzyme-based functional assignments of short-chain dehydrogenases/reductases (SDRs). Chem. Biol. Interact. 143-144, 271-8