ArticleNature chemical biology2020
Human PLD structures enable drug design and characterization of isoenzyme selectivity.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Phospholipases D: An Update on Structure-Function Relationships.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Non-specific phospholipase Cs and their potential for crop improvement.Journal of experimental botany · 2026Review
- Designing New Natural-Mimetic Phosphatidic Acid: A Versatile and Innovative Synthetic Strategy for Glycerophospholipid Research.Angewandte Chemie (International ed. in English) · 2025Article
- Development and Evaluation of Indole-Based Phospholipase D Inhibitors for Lung Cancer Immunotherapy.Journal of medicinal chemistry · 2025Article
- Phospholipase D1 is a critical mediator of neutrophil extracellular trap formation and venous thrombosis.Frontiers in immunology · 2025Article
- Crystal structure of Alzheimer's disease phospholipase D3 provides a molecular basis for understanding its normal and pathological functions.The FEBS journal · 2024Article
- Structure of human phospholipase D3, a single-strand exonuclease associated with Alzheimer's disease.The FEBS journal · 2024Article
- PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways.Experimental & molecular medicine · 2024Review
- Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4.Structure (London, England : 1993) · 2024Article
- Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation.Nucleic acids research · 2024Article
- Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA.Nature communications · 2022Article
- A New Phospholipase D fromInternational journal of molecular sciences · 2022Article
- Inhibition of phospholipase D1 induces immunogenic cell death and potentiates cancer immunotherapy in colorectal cancer.Experimental & molecular medicine · 2022Article
- Discovery of Phospholipase D Inhibitors with Improved Drug-like Properties and Central Nervous System Penetrance.ACS medicinal chemistry letters · 2022Article
- Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling.The Journal of biological chemistry · 2022Article
- Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors inFrontiers in microbiology · 2022Article
- PLD1 promotes reactive oxygen species production in vascular smooth muscle cells and injury-induced neointima formation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Crystal Structure of a Phospholipase D from the Plant-Associated BacteriaInternational journal of molecular sciences · 2021Article
- Structure and regulation of human phospholipase D.Advances in biological regulation · 2021Review
- Illustrating human PLD.Nature chemical biology · 2020Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipase D enzymes (PLDs) are ubiquitous phosphodiesterases that produce phosphatidic acid (PA), a key second messenger and biosynthetic building block. Although an orthologous bacterial Streptomyces sp. strain PMF PLD structure was solved two decades ago, the molecular basis underlying the functions of the human PLD enzymes (hPLD) remained unclear based on this structure due to the low homology between these sequences. Here, we describe the first crystal structures of hPLD1 and hPLD2 catalytic domains and identify novel structural elements and functional differences between the prokaryotic and eukaryotic enzymes. Furthermore, structure-based mutation studies and structures of inhibitor-hPLD complexes allowed us to elucidate the binding modes of dual and isoform-selective inhibitors, highlight key determinants of isoenzyme selectivity and provide a basis for further structure-based drug discovery and functional characterization of this therapeutically important superfamily of enzymes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.