7OFT

Structure of SARS-CoV-2 Papain-like protease PLpro in complex with p-hydroxybenzaldehyde


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease.

Srinivasan, V.Brognaro, H.Prabhu, P.R.de Souza, E.E.Gunther, S.Reinke, P.Y.A.Lane, T.J.Ginn, H.Han, H.Ewert, W.Sprenger, J.Koua, F.H.M.Falke, S.Werner, N.Andaleeb, H.Ullah, N.Franca, B.A.Wang, M.Barra, A.L.C.Perbandt, M.Schwinzer, M.Schmidt, C.Brings, L.Lorenzen, K.Schubert, R.Machado, R.R.G.Candido, E.D.Oliveira, D.B.L.Durigon, E.L.Niebling, S.Garcia, A.S.Yefanov, O.Lieske, J.Gelisio, L.Domaracky, M.Middendorf, P.Groessler, M.Trost, F.Galchenkova, M.Mashhour, A.R.Saouane, S.Hakanpaa, J.Wolf, M.Alai, M.G.Turk, D.Pearson, A.R.Chapman, H.N.Hinrichs, W.Wrenger, C.Meents, A.Betzel, C.

(2022) Commun Biol 5: 805-805

  • DOI: https://doi.org/10.1038/s42003-022-03737-7
  • Primary Citation of Related Structures:  
    7NFV, 7OFS, 7OFT, 7OFU

  • PubMed Abstract: 

    SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host's innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.


  • Organizational Affiliation

    Department of Chemistry, Institute of Biochemistry and Molecular Biology, Laboratory for Structural Biology of Infection and Inflammation, Universität Hamburg, Build. 22a, c/o DESY, 22607, Hamburg, Germany. [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Papain-like protease nsp3315Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
EC: 3.4.19.12 (PDB Primary Data), 3.4.22 (PDB Primary Data)
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HBA (Subject of Investigation/LOI)
Query on HBA

Download Ideal Coordinates CCD File 
K [auth A]P-HYDROXYBENZALDEHYDE
C7 H6 O2
RGHHSNMVTDWUBI-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
L [auth A],
M [auth A]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.613α = 90
b = 81.613β = 90
c = 134.378γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research Foundation (DFG)GermanyEXC 2056 - project ID 390715994
European CommissionEuropean UnionEU project 101003551 - EXSCALATE4CoV (E4C)

Revision History  (Full details and data files)

  • Version 1.0: 2021-05-12
    Type: Initial release
  • Version 2.0: 2021-11-24
    Type: Coordinate replacement
    Reason: Model completeness
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Other, Refinement description, Structure summary
  • Version 2.1: 2022-09-07
    Changes: Database references, Structure summary
  • Version 2.2: 2024-01-31
    Changes: Data collection, Refinement description