Abstract 1525 A dynamic dehydrogenase: structural analysis of the carboxyspermidine dehydrogenase catalytic cycle

Polyamines play key roles in cellular growth and proliferation, with excess production linked to various types of cancer. In this study, carboxyspermidine dehydrogenase (CASDH), which is used by ∼70% of human gut microbes in the production of the polyamine spermidine, was examined. CASDH performs a NADPH-dependent reductive condensation of aspartate semi-aldehyde and putrescine to produce carboxyspermidine (CSP). A 2.5 Å structure of apo CASDH from Clostridium leptum was determined. Structural analysis revealed significant differences between apo ClCASDH and our previously solved NADP+ bound CASDH from Bacteroides fragilis.