5RLI

PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 helicase in complex with Z45617795


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase.

Newman, J.A.Douangamath, A.Yadzani, S.Yosaatmadja, Y.Aimon, A.Brandao-Neto, J.Dunnett, L.Gorrie-Stone, T.Skyner, R.Fearon, D.Schapira, M.von Delft, F.Gileadi, O.

(2021) Nat Commun 12: 4848-4848

  • DOI: https://doi.org/10.1038/s41467-021-25166-6
  • Primary Citation of Related Structures:  
    5RL6, 5RL7, 5RL8, 5RL9, 5RLB, 5RLC, 5RLD, 5RLE, 5RLF, 5RLG, 5RLH, 5RLI, 5RLJ, 5RLK, 5RLL, 5RLM, 5RLN, 5RLO, 5RLP, 5RLQ, 5RLR, 5RLS, 5RLT, 5RLU, 5RLV, 5RLW, 5RLY, 5RLZ, 5RM0, 5RM1, 5RM2, 5RM3, 5RM4, 5RM5, 5RM6, 5RM7, 5RM8, 5RM9, 5RMA, 5RMB, 5RMC, 5RMD, 5RME, 5RMF, 5RMG, 5RMH, 5RMI, 5RMJ, 5RMK, 5RML

  • PubMed Abstract: 

    There is currently a lack of effective drugs to treat people infected with SARS-CoV-2, the cause of the global COVID-19 pandemic. The SARS-CoV-2 Non-structural protein 13 (NSP13) has been identified as a target for anti-virals due to its high sequence conservation and essential role in viral replication. Structural analysis reveals two "druggable" pockets on NSP13 that are among the most conserved sites in the entire SARS-CoV-2 proteome. Here we present crystal structures of SARS-CoV-2 NSP13 solved in the APO form and in the presence of both phosphate and a non-hydrolysable ATP analog. Comparisons of these structures reveal details of conformational changes that provide insights into the helicase mechanism and possible modes of inhibition. To identify starting points for drug development we have performed a crystallographic fragment screen against NSP13. The screen reveals 65 fragment hits across 52 datasets opening the way to structure guided development of novel antiviral agents.


  • Organizational Affiliation

    Centre for Medicines Discovery, University of Oxford, Oxford, UK. Joseph.Newman@cmd.ox.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Helicase
A, B
601Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
EC: 3.6.4.12 (PDB Primary Data), 3.6.4.13 (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
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
JFM (Subject of Investigation/LOI)
Query on JFM

Download Ideal Coordinates CCD File 
C [auth A],
I [auth B],
J [auth B]
N-(2-phenylethyl)methanesulfonamide
C9 H13 N O2 S
JGDDFCYMSLNOGJ-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
N [auth B],
O [auth B]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
K [auth B]
L [auth B]
D [auth A],
E [auth A],
F [auth A],
K [auth B],
L [auth B],
M [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.846α = 102.88
b = 70.009β = 95.84
c = 84.938γ = 112.37
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-30
    Type: Initial release
  • Version 1.1: 2022-09-07
    Changes: Database references
  • Version 1.2: 2024-05-22
    Changes: Data collection