RCSB PDB - 5S33: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with Z906021418

 5S33

PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with Z906021418


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.06 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 

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Ligand Structure Quality Assessment 

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Literature

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.

Schuller, M.Correy, G.J.Gahbauer, S.Fearon, D.Wu, T.Diaz, R.E.Young, I.D.Carvalho Martins, L.Smith, D.H.Schulze-Gahmen, U.Owens, T.W.Deshpande, I.Merz, G.E.Thwin, A.C.Biel, J.T.Peters, J.K.Moritz, M.Herrera, N.Kratochvil, H.T.Aimon, A.Bennett, J.M.Brandao Neto, J.Cohen, A.E.Dias, A.Douangamath, A.Dunnett, L.Fedorov, O.Ferla, M.P.Fuchs, M.R.Gorrie-Stone, T.J.Holton, J.M.Johnson, M.G.Krojer, T.Meigs, G.Powell, A.J.Rack, J.G.M.Rangel, V.L.Russi, S.Skyner, R.E.Smith, C.A.Soares, A.S.Wierman, J.L.Zhu, K.O'Brien, P.Jura, N.Ashworth, A.Irwin, J.J.Thompson, M.C.Gestwicki, J.E.von Delft, F.Shoichet, B.K.Fraser, J.S.Ahel, I.

(2021) Sci Adv 7

  • DOI: https://doi.org/10.1126/sciadv.abf8711
  • Primary Citation of Related Structures:  
    5RS7, 5RS8, 5RS9, 5RSB, 5RSC, 5RSD, 5RSE, 5RSF, 5RSG, 5RSH, 5RSI, 5RSJ, 5RSK, 5RSL, 5RSM, 5RSN, 5RSO, 5RSP, 5RSQ, 5RSR, 5RSS, 5RST, 5RSU, 5RSV, 5RSW, 5RSX, 5RSY, 5RSZ, 5RT0, 5RT1, 5RT2, 5RT3, 5RT4, 5RT5, 5RT6, 5RT7, 5RT8, 5RT9, 5RTA, 5RTB, 5RTC, 5RTD, 5RTE, 5RTF, 5RTG, 5RTH, 5RTI, 5RTJ, 5RTK, 5RTL

  • PubMed Abstract: 

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.


  • Organizational Affiliation

    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Non-structural protein 3
A, B
169Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
EC: 3.4.22
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
K2G (Subject of Investigation/LOI)
Query on K2G

Download Ideal Coordinates CCD File 
C [auth A]5-chloro-2-(propan-2-yl)pyrimidine-4-carboxamide
C8 H10 Cl N3 O
PCWKLVQVDIXCTG-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.06 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.243α = 90
b = 88.243β = 90
c = 39.114γ = 90
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 K2GClick on this verticalbar to view details

Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2021-01-13
    Type: Initial release
  • Version 1.1: 2021-01-27
    Changes: Structure summary
  • Version 1.2: 2021-07-07
    Changes: Database references
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references