{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin ES"],"funding":["National Science and Technology Council, Taiwan"],"pagination":["149"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9856072"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Dihydroorotase (DHOase) is the third enzyme in the pathway used for the biosynthesis of pyrimidine nucleotides. In mammals, DHOase is active in a trifunctional enzyme, CAD, which also carries out the activities of carbamoyl phosphate synthetase and aspartate transcarbamoylase. Prior to this study, it was unknown whether the FDA-approved clinical drug 5-fluorouracil (5-FU), which is used as an anticancer therapy, could bind to the DHOase domain of human CAD (huDHOase). Here, we identified huDHOase as a new 5-FU binding protein, thereby extending the 5-FU interactome to this human enzyme. In order to investigate where 5-FU binds to huDHOase, we solved the complexed crystal structure at 1.97 Å (PDB ID 8GVZ). The structure of huDHOase complexed with malate was also determined for the sake of c"],"journal":["Biomolecules"],"pubmed_title":["Complexed Crystal Structure of the Dihydroorotase Domain of Human CAD Protein with the Anticancer Drug 5-Fluorouracil."],"pmcid":["PMC9856072"],"funding_grant_id":["NSTC 111-2622-E-025-002"],"pubmed_authors":["Huang YH","Lin ES","Peng WF","Huang CY","Yang PC"],"additional_accession":[]},"is_claimable":false,"name":"Complexed Crystal Structure of the Dihydroorotase Domain of Human CAD Protein with the Anticancer Drug 5-Fluorouracil.","description":"Dihydroorotase (DHOase) is the third enzyme in the pathway used for the biosynthesis of pyrimidine nucleotides. In mammals, DHOase is active in a trifunctional enzyme, CAD, which also carries out the activities of carbamoyl phosphate synthetase and aspartate transcarbamoylase. Prior to this study, it was unknown whether the FDA-approved clinical drug 5-fluorouracil (5-FU), which is used as an anticancer therapy, could bind to the DHOase domain of human CAD (huDHOase). Here, we identified huDHOase as a new 5-FU binding protein, thereby extending the 5-FU interactome to this human enzyme. In order to investigate where 5-FU binds to huDHOase, we solved the complexed crystal structure at 1.97 Å (PDB ID 8GVZ). The structure of huDHOase complexed with malate was also determined for the sake of c","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-04T10:21:25.566Z","creation":"2025-02-19T00:12:52.069Z"},"accession":"S-EPMC9856072","cross_references":{"pubmed":["36671534"],"doi":["10.3390/biom13010149"]}}