ANALYSIS OF THE STRUCTURE AND SUBSTRATE-BINDING OF PHORMIDIUM-LAPIDEUM ALANINE DEHYDROGENASE

The structure of the hexameric L-alanine dehydrogenase from Phormidium lapideum reveals that the subunit is constructed from two domains, ea ch having the common dinucleotide binding fold. Despite there being no sequence similarity, the fold of alanine dehydrogenase is closely rel ated to that of the family of D-2-hydroxyacid dehydrogenases, with a s imilar location of the active site, suggesting that these enzymes are related by divergent evolution. L-alanine dehydrogenase and the 2-hydr oxyacid dehydrogenases also use equivalent functional groups to promot e substrate recognition and catalysis. However, they are arranged diff erently on the enzyme surface, which has the effect of directing oppos ite faces of the keto acid to the dinucleotide in each case, forcing a change in absolute configuration of the product.