ArticleBiochemistry2017
The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan).
Article in Biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Dose-dependent structural and electron-density features in the lytic polysaccharide monooxygenase NcAA9D.Acta crystallographica. Section D, Structural biology · 2026Article
- How an overlooked gene in coenzyme a synthesis solved an enzyme mechanism predicament.Molecular microbiology · 2023Review
- DXP Synthase Function in a Bacterial Metabolic Adaptation and Implications for Antibacterial Strategies.Antibiotics (Basel, Switzerland) · 2023Article
- More than Meets the Eye: Untargeted Metabolomics and Lipidomics Reveal Complex Pathways Spurred by Activation of Acid Resistance Mechanisms inJournal of proteome research · 2022Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- Homogeneous batch micro-crystallization of proteins from ammonium sulfate.Acta crystallographica. Section D, Structural biology · 2021Article
- Stable pantothenamide bioisosteres: novel antibiotics for Gram-positive bacteria.The Journal of antibiotics · 2019Article
- Protein-Derived Cofactors Revisited: Empowering Amino Acid Residues with New Functions.Biochemistry · 2018Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The antimetabolite pentyl pantothenamide has broad spectrum antibiotic activity but exhibits enhanced activity against Escherichia coli. The PanDZ complex has been proposed to regulate the pantothenate biosynthetic pathway in E. coli by limiting the supply of β-alanine in response to coenzyme A concentration. We show that formation of such a complex between activated aspartate decarboxylase (PanD) and PanZ leads to sequestration of the pyruvoyl cofactor as a ketone hydrate and demonstrate that both PanZ overexpression-linked β-alanine auxotrophy and pentyl pantothenamide toxicity are due to formation of this complex. This both demonstrates that the PanDZ complex regulates pantothenate biosynthesis in a cellular context and validates the complex as a target for antibiotic development.
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