[English] 日本語
Yorodumi
- PDB-9nnp: Composite structure of HSV-1 helicase-primase in complex with a f... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9nnp
TitleComposite structure of HSV-1 helicase-primase in complex with a forked DNA
Components
  • DNA (5'-D(P*TP*AP*CP*AP*TP*AP*A)-3')
  • DNA helicase/primase complex-associated protein
  • DNA primase
  • DNA replication helicase
KeywordsTransferase/Hydrolase/DNA / DNA replication / HSV-1 helicase-primase / VIRAL PROTEIN / Transferase-Hydrolase-DNA complex
Function / homology
Function and homology information


bidirectional double-stranded viral DNA replication / helicase activity / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / DNA-directed RNA polymerase activity / DNA replication / hydrolase activity / host cell nucleus / zinc ion binding / ATP binding
Similarity search - Function
DNA replication helicase domain / DNA helicase/primase complex-associated protein / DNA replication helicase, Herpesvirus / Herpesvirus DNA helicase/primase complex associated protein / Helicase / DNA primase / Herpesviridae UL52/UL70 DNA primase / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
DNA / DNA (> 10) / DNA replication helicase / DNA helicase/primase complex-associated protein / DNA primase
Similarity search - Component
Biological speciesHuman alphaherpesvirus 1 strain 17
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsHe, Q. / Baranovskiy, A.G. / Morstadt, L.M. / Babayeva, N.D. / Lim, C. / Tahirov, T.H.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM152032 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)DP2GM150023 United States
CitationJournal: Sci Adv / Year: 2025
Title: Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir.
Authors: Andrey G Baranovskiy / Qixiang He / Yoshiaki Suwa / Lucia M Morstadt / Nigar D Babayeva / Ci Ji Lim / Tahir H Tahirov /
Abstract: Widespread herpesvirus infections are associated with various diseases. DNA replication of human herpes simplex virus type 1 (HSV-1) requires a helicase-primase (HP) complex of three core proteins: ...Widespread herpesvirus infections are associated with various diseases. DNA replication of human herpes simplex virus type 1 (HSV-1) requires a helicase-primase (HP) complex of three core proteins: UL5, UL52, and UL8. This complex unwinds viral DNA and synthesizes primers for DNA replication, making it an attractive antiviral target. Although HP inhibitors pritelivir and amenamevir were identified through screening, their binding mechanisms remain unclear. Here, we report cryo-electron microscopy structures of HSV-1 HP bound to a forked DNA template alone and in complex with pritelivir or amenamevir. The structures reveal a bilobed architecture highlighting HP coordinated action at the replication fork and providing a structural basis for HP inhibition by illustrating precisely how pritelivir and amenamevir block helicase activity. Data lay a solid foundation for the development of improved antiviral therapies.
History
DepositionMar 5, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 19, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA replication helicase
B: DNA primase
C: DNA helicase/primase complex-associated protein
D: DNA (5'-D(P*TP*AP*CP*AP*TP*AP*A)-3')
hetero molecules


Theoretical massNumber of molelcules
Total (without water)298,0216
Polymers297,8904
Non-polymers1312
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein DNA replication helicase


Mass: 95760.805 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human alphaherpesvirus 1 strain 17 / Gene: HELI, UL5 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P10189, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#2: Protein DNA primase


Mass: 114558.562 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human alphaherpesvirus 1 strain 17 / Gene: UL52 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P10236, Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases
#3: Protein DNA helicase/primase complex-associated protein / HEPA / Primase-associated factor


Mass: 80005.664 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human alphaherpesvirus 1 strain 17 / Gene: UL8 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P10192
#4: DNA chain DNA (5'-D(P*TP*AP*CP*AP*TP*AP*A)-3')


Mass: 7564.930 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: HSV-1 helicase-primase in complex with a forked DNA / Type: COMPLEX
Details: HSV-1 helicase-primase in complex with a forked DNAsovled using cryo-EM single-particle analysis
Entity ID: #1-#4 / Source: RECOMBINANT
Molecular weightValue: 0.3 MDa / Experimental value: NO
Source (natural)Organism: Human alphaherpesvirus 1 strain 17
Source (recombinant)Organism: Escherichia coli BL21(DE3) (bacteria)
Buffer solutionpH: 7.5
Details: CHAPSO is made fresh at 80 mM before being added to the sample at a final concentration of 4 mM immediately before vitrification
Buffer component
IDConc.NameFormulaBuffer-ID
120 mM2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acidHEPES1
2100 mMpotassium chlorideKCl1
30.5 percentGlycerolGlycerol1
42 mMdithiothreitolDTT1
54 mMCHAPSOCHAPSO1
SpecimenConc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: The sample was monodisperse
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277.15 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 12555

-
Processing

EM software
IDNameVersionCategory
2Latitudeimage acquisition
4cryoSPARCCTF correction
7Cootmodel fitting
9PHENIX1.21_5207:model refinement
10cryoSPARCinitial Euler assignment
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 4446980
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 431843 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Atomic model buildingSource name: AlphaFold / Type: in silico model
RefinementHighest resolution: 3.2 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00219990
ELECTRON MICROSCOPYf_angle_d0.51427284
ELECTRON MICROSCOPYf_dihedral_angle_d6.5192869
ELECTRON MICROSCOPYf_chiral_restr0.043077
ELECTRON MICROSCOPYf_plane_restr0.0053547

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more