Skip to main content


Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Figure 4 | BMC Structural Biology

Figure 4

From: Implications of the structure of human uridine phosphorylase 1 on the development of novel inhibitors for improving the therapeutic window of fluoropyrimidine chemotherapy

Figure 4

BAU binding to hUPP1. (A) BAU and phosphate coordination in hUPP1 is consistent with that previously observed in bacterial homologues with the notable exception that R64 (equivalent to R30 in E. coli) does not participate in phosphate binding, possessing instead a conformation that distances its guanidinium group from the negatively-charged oxygen atoms of the anion. (B) Shown is an alignment of three conformations of the E. coli enzyme with the two hUPP1 structures, focusing on the loop toward the back of the active site (human residues 278–284; boxed in Figure 2C). It has been hypothesized that in the bacterial enzyme, this loop undergoes an induced-fit conformational change upon ligand binding. In hUPP1, these residues are more ordered and conformationally restrained. They do not vary significantly in position between the BAU-bound and ligand-free structures, possibly due to the insertion of two additional residues within this region. These differences become increasingly important when considering the impacts of chemical modifications to the initial benzyl moiety of BAU, such as the characterized UPP inhibitor, 5-m-benzyloxybenzylacyclouridine (BBAU) shown (shaded).

Back to article page