Enzymes in Thymidylate Synthesis in Ureaplasma parvum as Medical Targets

摘要: The wall less bacterium Ureaplasma parvum (Up) is associated with ureathritis in adults and pneumonia neonates. Up lack de novo nucleotide synthesis genes has to import all DNA precursors. This thesis investigates known biosynthesis pathways as targets for new antibiotics concerns two enzymes thymidylate synthesis; a synthase (TS) thymidine kinase (UpTK). TS activity was detected Up-extracts UU572 could rescue mutant E. coli. appeared be proteolytic cleaved cell cycle regulated Up. Codon modified cloned expression However, no protein detected. A codon optimized synthesized homolog; MPN358 from Mycoplasma expressed coli showed activity. Low sequence homology existing TSs suggests that its homologs, belong class of enzymes, which may contribute future antibiotic development human veterinary medicine. Thirteen click chemistry-synthesized 3´-triazole analogs (1-13), using AZT backbone, were evaluated UpTK hTK1. bacterial TK exhibited more open 3D structure than hTK1 explaining substrate efficiency, while seemed have closed reflected by higher inhibition the analogs. Docking models 13 TK1 structures revealed amino acid substitutions active site most likely explain different enzyme specificity. In addition, molecular docking 6-fold nucleoside analog 3´-azido-methyl-deoxythymidine (AZMT) compared Nucleoside been used fighting viruses minimal side-effects. Why not use this strategy control infections? results presented towards attaining goal.