Structural homologies with ATP- and folate-binding enzymes in the crystal structure of folylpolyglutamate synthetase

摘要: Folylpolyglutamate synthetase, which is responsible for the addition of a polyglutamate tail to folate and derivatives, an ATP-dependent enzyme isolated from eukaryotic bacterial sources, where it plays key role in retention intracellular pool. Here, we report 2.4-A resolution crystal structure MgATP complex Lactobacillus casei. The structural analysis reveals that folylpolyglutamate synthetase modular protein consisting two domains, one with typical mononucleotide-binding fold other strikingly similar folate-binding dihydrofolate reductase. We have located active site large interdomain cleft adjacent ATP-binding P-loop motif. Opposite this site, C domain, cavity likely be binding has been identified, inspection surrounding suggests glutamate substrate may project into site. A further feature well defined Omega loop, contributes both interactions. determination represents first step toward elucidation molecular mechanism polyglutamylation folates antifolates.