ArticleThe Journal of biological chemistry2019
Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
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- Integrated Multi-Omics and Spatial Transcriptomics Reveal GUK1 as a Prognostic Biomarker Regulated by the TP53-HSF1 Axis in Breast Cancer.Oncology research · 2026Article
- Comprehensive profiling of the catalytic conformations of human Guanylate kinase.Nature communications · 2025Article
- Retinal degeneration protein 3 mutants are associated with cell-cycle arrest and apoptosis.Cell death discovery · 2025Article
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- Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease.Annals of neurology · 2024Article
- The activation cascade of the broad-spectrum antiviral bemnifosbuvir characterized at atomic resolution.PLoS biology · 2024Article
- Proteomic changes in the hippocampus of large mammals after total-body low dose radiation.PloS one · 2024Article
- From network analysis to experimental validation: identification of regulators of non-muscle myosin II contractility using the folded-gastrulation signaling pathway.BMC molecular and cell biology · 2023Article
- Investigating Neuron Degeneration in Huntington's Disease Using RNA-Seq Based Transcriptome Study.Genes · 2023Article
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.Journal of medicinal chemistry · 2023Article
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.bioRxiv : the preprint server for biology · 2023Article
- Influence of Guanine-Based Purines on the Oxidoreductive Reactions Involved in Normal or Altered Brain Functions.Journal of clinical medicine · 2023Review
- Identifying potential metabolic tissue biomarkers for papillary thyroid cancer in different iodine nutrient regions.Endocrine · 2021Article
- Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system.Nature communications · 2021Article
- Structural organization of the C1b projection within the ciliary central apparatus.Journal of cell science · 2021Article
- FBA reveals guanylate kinase as a potential target for antiviral therapies against SARS-CoV-2.Bioinformatics (Oxford, England) · 2020Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human guanylate kinase (hGMPK) is the only known enzyme responsible for cellular GDP production, making it essential for cellular viability and proliferation. Moreover, hGMPK has been assigned a critical role in metabolic activation of antiviral and antineoplastic nucleoside-analog prodrugs. Given that hGMPK is indispensable for producing the nucleotide building blocks of DNA, RNA, and cGMP and that cancer cells possess elevated GTP levels, it is surprising that a detailed structural and functional characterization of hGMPK is lacking. Here, we present the first high-resolution structure of hGMPK in the apo form, determined with NMR spectroscopy. The structure revealed that hGMPK consists of three distinct regions designated as the LID, GMP-binding (GMP-BD), and CORE domains and is in an open configuration that is nucleotide binding-competent. We also demonstrate that nonsynonymous single-nucleotide variants (nsSNVs) of the hGMPK CORE domain distant from the nucleotide-binding site of this domain modulate enzymatic activity without significantly affecting hGMPK's structure. Finally, we show that knocking down the
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