[English] 日本語
Yorodumi
- EMDB-49304: The rigid portion of Cryo-EM structure of Herpesvirus Helicase-Pr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-49304
TitleThe rigid portion of Cryo-EM structure of Herpesvirus Helicase-Primase complex with Pritelivir
Map data
Sample
  • Complex: The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex
    • Protein or peptide: DNA primase
    • Protein or peptide: DNA helicase/primase complex-associated protein
KeywordsInhibitor / Herpesvirus / Helicase / Primase / Pritelivir / REPLICATION / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


bidirectional double-stranded viral DNA replication / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / DNA-directed RNA polymerase activity / DNA replication / host cell nucleus / zinc ion binding
Similarity search - Function
DNA helicase/primase complex-associated protein / Herpesvirus DNA helicase/primase complex associated protein / DNA primase / Herpesviridae UL52/UL70 DNA primase
Similarity search - Domain/homology
DNA helicase/primase complex-associated protein / DNA primase
Similarity search - Component
Biological speciesHerpesviridae (virus)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsYao Q / Yu X
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Microbiol / Year: 2025
Title: Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors.
Authors: Qing Yao / Alexandre Mercier / Arabinda Nayak / Lindsey May / Pui Yan Ho / Ariel Lewis-Ballester / Varsha Nair / Annapurna Sapre / Thomas Aeschbacher / Jit Mukherjee / Christopher Richards / ...Authors: Qing Yao / Alexandre Mercier / Arabinda Nayak / Lindsey May / Pui Yan Ho / Ariel Lewis-Ballester / Varsha Nair / Annapurna Sapre / Thomas Aeschbacher / Jit Mukherjee / Christopher Richards / Roberto Mateo / Aesop Cho / Eric Lansdon / Xinchao Yu /
Abstract: The herpes simplex virus (HSV) helicase-primase (HP) complex is a promising anti-herpes therapeutic target. However, progress in developing highly effective small-molecule HP inhibitors (HPIs) for ...The herpes simplex virus (HSV) helicase-primase (HP) complex is a promising anti-herpes therapeutic target. However, progress in developing highly effective small-molecule HP inhibitors (HPIs) for the treatment of genital herpes has been hindered by the lack of structural information on the HP complex and the incomplete understanding of the mechanism of action of HPIs. Here we present the cryogenic electron microscopy structure of the HSV-1 HP apo-complex (3.8 Å), along with structures bound to pritelivir (3.2 Å) and amenamevir (3.2 Å)-two clinically active, chemically distinct HPIs. The potency of both inhibitors against HSV variants bearing mutations within the HPI binding pocket supports the high-resolution mapping of key molecular interactions while revealing residues that govern their antiviral spectrum against alphaherpesviruses. Our results provide important insight into the unique architecture of the HP complex and the mechanism of inhibition of HPIs, paving the way for the development of next-generation antivirals to treat herpesvirus infections.
History
DepositionFeb 19, 2025-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateFeb 25, 2026-
Current statusFeb 25, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_49304.png

Downloads & links

-
Map

FileDownload / File: emd_49304.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 440 pix.
= 320.76 Å		0.73 Å/pix.
x 440 pix.
= 320.76 Å		0.73 Å/pix.
x 440 pix.
= 320.76 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.729 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.133
Minimum - Maximum-0.0018010587 - 2.1848068
Average (Standard dev.)0.00060534663 (±0.019488262)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 320.75998 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_49304_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_49304_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_49304_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex

EntireName: The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex
Components
  • Complex: The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex
    • Protein or peptide: DNA primase
    • Protein or peptide: DNA helicase/primase complex-associated protein

-
Supramolecule #1: The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex

SupramoleculeName: The ternary complex of HSV-1 UL8/UL52/UL5 helicase-primase complex
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Herpesviridae (virus)

-
Macromolecule #1: DNA primase

MacromoleculeName: DNA primase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
EC number: Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases
Source (natural)Organism: Herpesviridae (virus)
Molecular weightTheoretical: 114.544547 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGQEDGNRGE RRAAGTPVEV TALYATDGCV ITSSIALLTN SLLGAEPVYI FSYDAYTHDG RADGPTEQDR FEESRALYQA SGGLNGDSF RVTFCLLGTE VGGTHQARGR TRPMFVCRFE RADDVAALQD ALAHGTPLQP DHIAATLDAE ATFALHANMI L ALTVAINN ...String:
MGQEDGNRGE RRAAGTPVEV TALYATDGCV ITSSIALLTN SLLGAEPVYI FSYDAYTHDG RADGPTEQDR FEESRALYQA SGGLNGDSF RVTFCLLGTE VGGTHQARGR TRPMFVCRFE RADDVAALQD ALAHGTPLQP DHIAATLDAE ATFALHANMI L ALTVAINN ASPRTGRDAA AAQYDQGASL RSLVGRTSLG QRGLTTLYVH HEVRVLAAYR RAYYGSAQSP FWFLSKFGPD EK SLVLTTR YYLLQAQRLG GAGATYDLQA IKDICATYAI PHAPRPDTVS AASLTSFAAI TRFCCTSQYA RGAAAAGFPL YVE RRIAAD VRETSALEKF ITHDRSCLRV SDREFITYIY LAHFECFSPP RLATHLRAVT THDPNPAAST EQPSPLGREA VEQF FCHVR AQLNIGEYVK HNVTPRETVL DGDTAKAYLR ARTYAPGALT PAPAYCGAVD SATKMMGRLA DAEKLVPRRG WPAFA PASP GEDTAGGTPP PQTCGIVKRL LRLAATEQQG PTPPAIAALI RNAAVQTPLP VYRISMVPTG QAFAALAWDD WARITR DAR LAEAVVSAEA AAHPDHGALG RRLTDRIRAQ GPVMPPGGLD AGGQMYVNRN EIFNGALAIT NIILDLDIAL KEPVPFR RL HEALGHFRRG ALAAVQLLFP AARVDPDAYP CYFFKSACRP GPASVGSGSG LGNDDDGDWF PCYDDAGDEE WAEDPGAM D TSHDPPDDEV AYFDLCHEVG PTAEPRETDS PVCSCTDKIG LRVCMPVPAP YVVHGSLTMR GVARVIQQAV LLDDFVVEA IGSYVKNFLL IDTGVYAHGH SLRLPYFAKI APDGPACGRL LPVFVIPPAC KDVPAFVAAH ADPRRFHFHA PPTYLASPRE IRVLHSLGG DYVSFFERKA SRNALEHFGR RETLTEVLGR YNVQPDAGGT VEGFASELLG RIVACIETHF PEHAGEYQAV S VRRAVSKD DWVLLQLVPV RGTLQQSLSC LRFKHGRASR ATARTFVALS VGANNRLCVS LCQQCFAAKC DSNRLHTLFT ID AGTPCSP SVPCSTSQPS S

UniProtKB: DNA primase

-
Macromolecule #2: DNA helicase/primase complex-associated protein

MacromoleculeName: DNA helicase/primase complex-associated protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Herpesviridae (virus)
Molecular weightTheoretical: 80.005664 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MDTADIVWVE ESVSAITLYA VWLPPRAREY FHALVYFVCR NAAGEGRARF AEVSVTATEL RDFYGSADVS VQAVVAAARA ATTPAASPL EPLENPTLWR ALYACVLAAL ERQTGPVALF APLRIGSDPR TGLVVKVERA SWGPPAAPRA ALLVAEANID I DPMALAAR ...String:
MDTADIVWVE ESVSAITLYA VWLPPRAREY FHALVYFVCR NAAGEGRARF AEVSVTATEL RDFYGSADVS VQAVVAAARA ATTPAASPL EPLENPTLWR ALYACVLAAL ERQTGPVALF APLRIGSDPR TGLVVKVERA SWGPPAAPRA ALLVAEANID I DPMALAAR VAEHPDARLA WARLAAIRDT PQCASAASLT VNITTGTALF AREYQTLAFP PIKKEGAFGD LVEVCEVGLR PR GHPQRVT ARVLLPRDYD YFVSAGEKFS APALVALFRQ WHTTVHAAPG ALAPVFAFLG PEFEVRGGPV PYFAVLGFPG WPT FTVPAT AESARDLVRG AAAAYAALLG AWPAVGARVV LPPRAWPGVA SAAAGCLLPA VREAVARWHP ATKIIQLLDP PAAV GPVWT ARFCFPGLRA QLLAALADLG GSGLADPHGR TGLARLDALV VAAPSEPWAG AVLERLVPDT CNACPALRQL LGGVM AAVC LQIEETASSV KFAVCGGDGG AFWGVFNVDP QDADAASGVI EDARRAIETA VGAVLRANAV RLRHPLCLAL EGVYTH AVA WSQAGVWFWN SRDNTDHLGG FPLRGPAYTT AAGVVRDTLR RVLGLTTACV PEEDALTARG LMEDACDRLI LDAFNKR LD AEYWSVRVSP FEASDPLPPT AFRGGALLDA EHYWRRVVRV CPGGGESVGV PVDLYPRPLV LPPVDCAHHL REILREIE L VFTGVLAGVW GEGGKFVYPF DDKMSFLFA

UniProtKB: DNA helicase/primase complex-associated protein

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.5 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average exposure time: 5.84 sec. / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 165000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 136652
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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