ArticleInternational journal of biological macromolecules2019
Pyrimidine biosynthesis in pathogens - Structures and analysis of dihydroorotases from Yersinia pestis and Vibrio cholerae.
Article in International journal of biological macromolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
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- Crystal structure of Methanococcus jannaschii dihydroorotase with substrate bound.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Conformational Dynamics of the Active Site Loop in Dihydroorotase Highlighting the Limitations of Loop-In Structures for Inhibitor Docking.International journal of molecular sciences · 2025Article
- Chemical Synthetic Lethality Screens Identify Selective Drug Combinations againstACS chemical biology · 2025Article
- The Loop-In Binding Mode of Dihydroorotase: Implications for Ligand Binding and Therapeutic Targeting.International journal of molecular sciences · 2025Review
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- Duodenal Metatranscriptomics to Define Human and Microbial Functional Alterations Associated with Severe Obesity: A Pilot Study.Microorganisms · 2020Article
- Molstack: A platform for interactive presentations of electron density and cryo-EM maps and their interpretations.Protein science : a publication of the Protein Society · 2020Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The de novo pyrimidine biosynthesis pathway is essential for the proliferation of many pathogens. One of the pathway enzymes, dihydroorotase (DHO), catalyzes the reversible interconversion of N-carbamoyl-l-aspartate to 4,5-dihydroorotate. The substantial difference between bacterial and mammalian DHOs makes it a promising drug target for disrupting bacterial growth and thus an important candidate to evaluate as a response to antimicrobial resistance on a molecular level. Here, we present two novel three-dimensional structures of DHOs from Yersinia pestis (YpDHO), the plague-causing pathogen, and Vibrio cholerae (VcDHO), the causative agent of cholera. The evaluations of these two structures led to an analysis of all available DHO structures and their classification into known DHO types. Comparison of all the DHO active sites containing ligands that are listed in DrugBank was facilitated by a new interactive, structure-comparison and presentation platform. In addition, we examined the genetic context of characterized DHOs, which revealed characteristic patterns for different types of DHOs. We also generated a homology model for DHO from Plasmodium falciparum.
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Registered trials
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