10ho | pdb_000010ho

Crystal structure of alkaline nuclease from Herpes simplex virus-1

spinqualitylabelsall models 10ho, resolution 2.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 10ho is a 1 chain structure with sequence from Human alphaherpesvirus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.46Å Ligands: ACT, FMT, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Herpes simplex virus 1 (HSV-1) UL12 encodes a highly conserved 5' --> 3' alkaline exonuclease that is essential for the production of infectious virus. Together with the viral single-stranded DNA-binding/annealing protein ICP8, UL12 functions as a two-component recombinase that mediates recombination-dependent viral DNA replication. Here, we present the crystal structure of the catalytic domain of the HSV alkaline nuclease (UL12), which provides the first view of an alpha-herpesvirus alkaline nuclease. Using this structure, we optimized a series of small-molecule viral nuclease inhibitors (VNIs) that target the UL12 active site and potently inhibit UL12 exonuclease activity in vitro. We have thus established a robust platform for structure-based docking, SAR analysis and rational inhibitor design. Because UL12 orthologs are conserved across all human herpesviruses, we examined the activity of these compounds against the beta- and gamma-herpesvirus alkaline nucleases UL98 and SOX and found that they inhibit all three enzymes. The VNIs also exhibit antiviral activity against HSV-1 and HCMV in cell culture. EC50 and IC50 values were in the nanomolar to low micromolar range. Together, these findings establish herpesvirus alkaline nucleases as conserved, druggable antiviral targets and provide a foundation for the development of broad-spectrum anti-herpesvirus therapeutics, either as standalone agents or in combination with existing nucleoside analogs. Viral Nuclease Inhibitors: Small molecule disruptors of the UL12 alkaline nuclease display broad anti-herpes virus activity.,Sharma N, Xie X, Szczepaniak R, Rani C, Khosro SK, Krucinska J, Chen X, Do D, Wright L, Wright D, Weller S PLoS Pathog. 2026 Aug 17;22(8):e1014531. doi: 10.1371/journal.ppat.1014531. , eCollection 2026 Aug. PMID:42607086 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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