Short-chain dehydrogenases/reductases (SDR) constitute a large protein fami
ly. The SDR family now includes more than 1,000 enzymes from humans, mammal
s, insects and bacteria, and exhibits a wide variety of substrate specifici
ty for steroids, retinoids, prostaglandins, sugars, alcohols and other smal
l molecules. These enzymes have a residue identity level of 15-30 %. Much h
as been done in the last decade to understand the structure-function relati
onships in the SDR enzymes. This review summarizes recent progress of struc
tural and functional studies of the enzymes belonging to the SDR family (X-
ray crystal structure analyses and site-directed mutagenesis studies). Base
d on these studies, the three-dimensional structure, catalytic mechanism, c
oenzyme specificity, and substrate specificity of the SDR enzymes are discu
ssed.