Slime mold, plant and insect dihydropyrimidine amidohydrolases (DHPases, EC 3.5.2.2), which catalyze the second step of pyrimidine and several anti-cancer drug degradations, were cloned and shown to functionally replace a defective DHPase enzyme in the yeast Saccharomyces kluyveri. The yeast and slime mold DHPases were over-expressed, shown to contain two zinc ions, characterized for their properties and compared to those of the calf liver enzyme. In general, the kinetic parameters varied widely among the enzymes, the mammalian DHPase having the highest catalytic efficiency. The ring opening was catalyzed most efficiently at pH 8.0 and competitively inhibited by the reaction product, N-carbamyl-beta-alanine. At lower pH values DHPases catalyzed the reverse reaction, the closing of the ring. Apparently, eukaryote DHPases are enzymatically as well as phylogenetically related to the de novo biosynthetic dihydroorotase (DHOase) enzymes. Modeling studies showed that the position of the catalytically critical amino acid residues of bacterial DHOases and eukaryote DHPases overlap. Therefore, only a few modifications might have been necessary during evolution to convert the unspecialized enzyme into anabolic and catabolic ones.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC152861 | PMC |
| http://dx.doi.org/10.1093/nar/gkg258 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dihydropyrimidinase deficiency with atrioventricular septal defect: a case report.
J Pediatr Endocrinol Metab
August 2024
Division of Pediatric Neurology, Department of Pediatrics, Hacettepe University İhsan Doğramacı Children's Hospital, Ankara, Türkiye.
Objectives: Dihydropyrimidinase deficiency is a rare autosomal recessive disorder of the pyrimidine degradation pathway, with fewer than 40 patients published. Clinical findings are variable and some patients may remain asymptomatic. Global developmental delay and increased susceptibility to 5-fluorouracil are commonly reported.
View Article and Find Full Text PDFSynthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole-Tetrahydropyrimidinone(thione) Hybrid Scaffolds as Urease Inhibitors.
Chem Biodivers
May 2023
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, 9138813944, Mashhad, Iran.
New series of triazole-tetrahydropyrimidinone(thione) hybrids (9a-g) were synthesized. FT-IR, H-NMR, C-NMR, elemental analysis and mass spectroscopic studies characterized the structures of the synthesized compounds. Then, the synthesized compounds were screened to determine the urease inhibitory activity.
View Article and Find Full Text PDFDesign, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors.
Arch Pharm (Weinheim)
October 2022
Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
The urease enzyme, a metalloenzyme having Ni ions, is recognized in some bacteria, fungi, and plants. Particularly, it is vital to the progress of infections induced by pathogenic microbes, such as Proteus mirabilis and Helicobacter pylori. Herein, we reported the synthesis of a series of tetrahydropyrimidine derivatives and evaluated their antiurease activity.
View Article and Find Full Text PDFSynthesis of dihydropyrimidine stabilized silver nanoparticles with significant anti urease and catalytic applications.
Pak J Pharm Sci
May 2022
Department of Chemistry, NED University of Engineering and Technology, Karachi, Pakistan.
We synthesized and explored biological and environmental applications of novel silver nanoparticles (AgNps) stabilized by short chain heterocyclic thiol namely Ethyl 6-methyl-4-phenyl-2-thioxo1,2,3,4-dihydropyrim-idine-5-carboxylate (DHPM). Dihydropyrimidines (DHPM), a biological active class of compounds that contain a single thiol group at the focal point which strongly stabilized the nascent AgNps. The short alkyl chain of (DHPM) effectively controlled the growth kinetics and surface morphology of AgNps.
View Article and Find Full Text PDFDiscovery of Novel Dihydropyrimidine and hydroxamic acid hybrids as potent Helicobacter pylori Urease inhibitors.
Bioorg Chem
September 2021
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India. Electronic address:
Two novel series of Dihydropyrimidine-hydroxamic acid hybrids (4a-4l and 5a-5l) were designed, synthesized and evaluated for in vitro Helicobacter pylori urease inhibition. In vitro enzyme inhibition screening led to the discovery of three potent urease inhibitors 2-[[4-(4-hydroxy phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy acetamide (4g), 2-[[4-(4-chloro phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy acetamide (4b) and 3-[[4-(3-methoxy phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy propanamide (5l). Compound 4g showed excellent urease inhibition with IC value of 14 ± 1 nM, indicated by its strong interactions with both metallic Ni ions, Gly279, His221, Ala365, Asp362, Asn168, Arg338 and His322 residues of the active site of urease.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!