RCSB PDB - 5SA7: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z1673618163

 5SA7

PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z1673618163


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

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Ligand Structure Quality Assessment 

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Literature

Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease.

Godoy, A.S.Nakamura, A.M.Douangamath, A.Song, Y.Noske, G.D.Gawriljuk, V.O.Fernandes, R.S.Pereira, H.D.M.Oliveira, K.I.Z.Fearon, D.Dias, A.Krojer, T.Fairhead, M.Powell, A.Dunnet, L.Brandao-Neto, J.Skyner, R.Chalk, R.Bajusz, D.Bege, M.Borbas, A.Keseru, G.M.von Delft, F.Oliva, G.

(2023) Nucleic Acids Res 

  • DOI: https://doi.org/10.1093/nar/gkad314
  • Primary Citation of Related Structures:  
    5S6X, 5S6Y, 5S6Z, 5S70, 5S71, 5S72, 5SA4, 5SA5, 5SA6, 5SA7, 5SA8, 5SA9, 5SAA, 5SAB, 5SAC, 5SAD, 5SAE, 5SAF, 5SAG, 5SAH, 5SAI, 5SBF, 7KEG, 7KEH, 7KF4, 7ME0, 7N7R, 7N7U, 7N7W, 7N7Y, 7N83, 7RB0, 7RB2

  • PubMed Abstract: 

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.


  • Organizational Affiliation

    Sao Carlos Institute of Physics, University of Sao Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos, 13563-120, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Uridylate-specific endoribonuclease
A, B
349Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
EC: 3.1
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
WL7 (Subject of Investigation/LOI)
Query on WL7

Download Ideal Coordinates CCD File 
C [auth A]4-amino-N-(2-hydroxyethyl)-N-methylbenzene-1-sulfonamide
C9 H14 N2 O3 S
IFBDYRCQPHERQI-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 150.201α = 90
b = 150.201β = 90
c = 111.033γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted WL7Click on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Fundacao de Amparo a Pesquisa do Estado de Sao PauloBrazil2013/07600-3

Revision History  (Full details and data files)

  • Version 1.0: 2021-06-09
    Type: Initial release
  • Version 1.1: 2023-05-10
    Changes: Database references
  • Version 1.2: 2024-05-22
    Changes: Data collection