7e3u | pdb_00007e3u

Crystal structure of the Pseudomonas aeruginosa dihydropyrimidinase complexed with 5-AU

spinqualitylabelsall models 7e3u, resolution 2.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7e3u is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: WBU, ZN NonStd Res: KCX Activity: Dihydropyrimidinase, with EC number 3.5.2.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HYDA_PSEAE] Catalyzes the hydrolysis of dihydropyrimidines and of the structurally related DL-5-mono-substituted hydantoins, to produce N-carbamoyl-D-amino acids. Publication Abstract from PubMed Dihydropyrimidinase (DHPase) is a key enzyme for pyrimidine degradation. DHPase contains a binuclear metal center in which two Zn ions are bridged by a posttranslationally carbamylated lysine. DHPase catalyzes the hydrolysis of dihydrouracil to N-carbamoyl-beta-alanine. Whether 5-aminouracil (5-AU), a thymine antagonist and an anticancer drug that can block DNA synthesis and induce replication stress, can interact with DHPase remains to be investigated. In this study, we determined the crystal structure of Pseudomonas aeruginosa DHPase (PaDHPase) complexed with 5-AU at 2.1 A resolution (PDB entry 7E3U). This complexed structure revealed that 5-AU interacts with Znalpha (3.2 A), Znbeta (3.0 A), the main chains of residues Ser289 (2.8 A) and Asn337 (3.3 A), and the side chain of residue Tyr155 (2.8 A). These residues are also known as the substrate-binding sites of DHPase. Dynamic loop I (amino acid residues Pro65-Val70) in PaDHPase is not involved in the binding of 5-AU. The fluorescence quenching analysis and site-directed mutagenesis were used to confirm the binding mode revealed by the complexed crystal structure. The 5-AU binding mode of PaDHPase is, however, different from that of 5-fluorouracil, the best-known fluoropyrimidine used for anticancer therapy. These results provide molecular insights that may facilitate the development of new inhibitors targeting DHPase and constitute the 5-AU interactome. Molecular Insights into How the Dimetal Center in Dihydropyrimidinase Can Bind the Thymine Antagonist 5-Aminouracil: A Different Binding Mode from the Anticancer Drug 5-Fluorouracil.,Lin ES, Luo RH, Yang YC, Huang CY Bioinorg Chem Appl. 2022 Feb 14;2022:1817745. doi: 10.1155/2022/1817745., eCollection 2022. PMID:35198016 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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