ArticleProceedings of the National Academy of Sciences of the United States of America2008
Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 81 citations in OpenAlex.
- RP101 (brivudine) binds to heat shock protein HSP27 (HSPB1) and enhances survival in animals and pancreatic cancer patients.Journal of cancer research and clinical oncology · 2011Trial
- Exploration of the protein and pharmacological landscape of monkeypox virus treatment: from entry point to end point.Molecular diversity · 2026Review
- Exploring drug repurposing for monkeypox virus: A structural and computational approach.Journal of Taibah University Medical Sciences · 2026Article
- Investigating Marine Natural Products as Potential Antivirals of Mpox Virus Replication by Targeting Thymidylate Kinase.ACS omega · 2026Article
- Structure-based multi-pocket virtual screening identifies FDA-approved candidate compounds targeting MPXV thymidylate kinase.Frontiers in cellular and infection microbiology · 2026Article
- Repurposing of FDA-Approved Antiviral Drugs Against Monkeypox Virus: Comparative In Vitro Screening and Structure Based In Silico Studies.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Virtual screening and identification of potent phytoconstituents from Acorus calamus L. as inhibitors of Monkeypox virus infection.Journal, genetic engineering & biotechnology · 2025Article
- Exploring the Dynamics ofCurrent medicinal chemistry · 2025Article
- Computational repurposing of polyphenols for anti-Mpoxviral activity.In silico pharmacology · 2025Article
- Identification of the myxobacterial secondary metabolites Aurachin A and Soraphinol A as promising inhibitors of thymidylate kinase of the Monkeypox virus.Molecular diversity · 2024Article
- Cheminformatics and machine learning approaches for repurposing anti-viral compounds against monkeypox virus thymidylate kinase.Molecular diversity · 2024Article
- Identification of core therapeutic targets for Monkeypox virus and repurposing potential of drugs: A WEB prediction approach.PloS one · 2024Article
- In silico identification of potential inhibitors of vital monkeypox virus proteins from FDA approved drugs.Molecular diversity · 2023Article
- Current Insights into Diagnosis, Prevention Strategies, Treatment, Therapeutic Targets, and Challenges of Monkeypox (Mpox) Infections in Human Populations.Life (Basel, Switzerland) · 2023Review
- Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus.Frontiers in cellular and infection microbiology · 2023Article
- Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study.International journal of molecular sciences · 2022Article
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- In Silico Repurposed Drugs against Monkeypox Virus.Molecules (Basel, Switzerland) · 2022Article
- In Silico Studies of Potential Selective Inhibitors of Thymidylate Kinase fromPharmaceuticals (Basel, Switzerland) · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike most DNA viruses, poxviruses replicate in the cytoplasm of host cells. They encode enzymes needed for genome replication and transcription, including their own thymidine and thymidylate kinases. Some herpes viruses encode only 1 enzyme catalyzing both reactions, a peculiarity used for prodrug activation to obtain maximum specificity. We have solved the crystal structures of vaccinia virus thymidylate kinase bound to TDP or brivudin monophosphate. Although the viral and human enzymes have similar sequences (42% identity), they differ in their homodimeric association and active-site geometry. The vaccinia TMP kinase dimer arrangement is orthogonal and not antiparallel as in human enzyme. This different monomer orientation is related to the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket. Consequently, the pox enzyme accommodates nucleotides with bulkier bases, like brivudin monophosphate and dGMP; these are efficiently phosphorylated and stabilize the enzyme. The brivudin monophosphate-bound structure explains the structural basis for this specificity, opening the way to the rational development of specific antipox agents that may also be suitable for poxvirus TMP kinase gene-based chemotherapy of cancer.
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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 OpenQuestion graph.