Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Dynamics of the Herpes simplex virus DNA polymerase holoenzyme during DNA synthesis and proof-reading revealed by Cryo-EM.
Journal, issue, pages	Nucleic Acids Res, Vol. 52, Issue 12, Page 7292-7304, Year 2024
Publish date	Jul 8, 2024
Authors	Emil Gustavsson / Kay Grünewald / Per Elias / B Martin Hällberg /
PubMed Abstract	Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 ...Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.
External links	Nucleic Acids Res / PubMed:38806233 / PubMed Central
Methods	EM (single particle)
Resolution	1.87 - 3.11 Å
Structure data	16906 8oj6 EMDB-16906, PDB-8oj6: HSV-1 DNA polymerase-processivity factor complex in pre-translocation state Method: EM (single particle) / Resolution: 2.41 Å 16907 8oj7 EMDB-16907, PDB-8oj7: HSV-1 DNA polymerase-processivity factor complex in halted elongation state Method: EM (single particle) / Resolution: 2.46 Å 16909 8oja EMDB-16909, PDB-8oja: HSV-1 DNA polymerase-processivity factor complex in exonuclease state Method: EM (single particle) / Resolution: 1.87 Å 16910 8ojb EMDB-16910, PDB-8ojb: HSV-1 DNA polymerase-processivity factor complex in exonuclease state active site Method: EM (single particle) / Resolution: 1.9 Å 16911 8ojc EMDB-16911, PDB-8ojc: HSV-1 DNA polymerase active site in alternative exonuclease state Method: EM (single particle) / Resolution: 2.08 Å 16912 8ojd EMDB-16912, PDB-8ojd: HSV-1 DNA polymerase beta-hairpin loop Method: EM (single particle) / Resolution: 2.46 Å EMDB-16918: Focused refinement map of HSV-1 DNA polymerase in pre-translocation state Method: EM (single particle) / Resolution: 2.4 Å EMDB-16919: Focused refinement map of HSV-1 DNA polymerase processivity factor in pre-translocation state Method: EM (single particle) / Resolution: 3.11 Å EMDB-16924: Focused refinement of HSV-1 DNA polymerase in halted elongation state Method: EM (single particle) / Resolution: 2.42 Å EMDB-16925: Focused refinement of HSV-1 DNA polymerase processivity factor in halted elongation state Method: EM (single particle) / Resolution: 2.97 Å EMDB-16927: Focused refinement map of HSV-1 DNA polymerase in exonuclease state Method: EM (single particle) / Resolution: 1.89 Å EMDB-16928: Focused refinement map of HSV-1 DNA polymerase processivity factor in exonuclease state Method: EM (single particle) / Resolution: 2.35 Å EMDB-17013: HSV-1 DNA polymerase-processivity factor complex in halted elongation state consensus map Method: EM (single particle) / Resolution: 2.4 Å EMDB-17014: Consensus map of HSV-1 DNA polymerase-processivity factor complex in pre-translocation state Method: EM (single particle) / Resolution: 2.41 Å EMDB-17018: Consensus map of HSV-1 DNA polymerase-processivity factor complex in exonuclease state Method: EM (single particle) / Resolution: 2.03 Å 19837 9enp EMDB-19837, PDB-9enp: HSV-1 DNA polymerase-processivity factor complex in exonuclease state with 1-bp DNA mismatch Method: EM (single particle) / Resolution: 2.12 Å 19838 9enq EMDB-19838, PDB-9enq: HSV-1 DNA polymerase-processivity factor complex in exonuclease state active site with 1-bp DNA mismatch Method: EM (single particle) / Resolution: 2.12 Å EMDB-19839: HSV-1 DNA polymerase-processivity factor complex in exonuclease state with 1-bp DNA mismatch consensus map Method: EM (single particle) / Resolution: 2.23 Å EMDB-19840: HSV-1 DNA polymerase-processivity factor complex in exonuclease state with 1-bp DNA mismatch catalytic core focused map Method: EM (single particle) / Resolution: 2.1 Å EMDB-19841: HSV-1 DNA polymerase-processivity factor complex in exonuclease state with 1-bp DNA mismatch processivity factor focused refinement Method: EM (single particle) / Resolution: 2.87 Å
Chemicals	ChemComp-MG: Unknown entry ChemComp-HOH: WATER ChemComp-DTP: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE ChemComp-CA: Unknown entry
Source	human alphaherpesvirus 1 strain kos synthetic construct (others)
Keywords	TRANSFERASE / DNA / Polymerase / Complex