5RLG

PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 helicase in complex with Z19739650

PDB DOI: https://doi.org/10.2210/pdb5RLG/pdb
Deposition Group: G_1002164 (changed state) ExploreG_1002164

Classification: VIRAL PROTEIN
Organism(s): Severe acute respiratory syndrome coronavirus 2
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2020-09-16 Released: 2020-09-30
Deposition Author(s): Newman, J.A., Yosaatmadja, Y., Douangamath, A., Aimon, A., Powell, A.J., Dias, A., Fearon, D., Dunnett, L., Brandao-Neto, J., Krojer, T., Skyner, R., Gorrie-Stone, T., Thompson, W., von Delft, F., Arrowsmith, C.H., Edwards, A., Bountra, C., Gileadi, O.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.96 Å
R-Value Free: 0.286
R-Value Work: 0.246
R-Value Observed: 0.248

wwPDB Validation 3D Report Full Report

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

PubMed: 34381037 Search on PubMedSearch on PubMed Central
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.

Macromolecule Content

Total Structure Weight: 134.82 kDa
Atom Count: 9,418
Modelled Residue Count: 1,157
Deposited Residue Count: 1,202
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Helicase	A [auth B], B [auth A]	601	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 0 Gene Names: rep, 1a-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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0DTD1
Sequence AnnotationsExpand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
VW1 (Subject of Investigation/LOI) Query on VW1 Download Ideal Coordinates CCD File SDF format, chain C [auth B] MOL2 format, chain C [auth B] mmCIF format, chain C [auth B]	C [auth B]	(2S)-2-(4-cyanophenoxy)propanamide C₁₀ H₁₀ N₂ O₂ JHIGQTTZYWLCKT-UHFFFAOYSA-N		Interactions Focus chain C [auth B] Interactions & Density Focus chain C [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain L [auth A] SDF format, chain M [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] mmCIF format, chain G [auth B] mmCIF format, chain H [auth B] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A]	G [auth B], H [auth B], L [auth A], M [auth A]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain G [auth B] Focus chain H [auth B] Focus chain L [auth A] Focus chain M [auth A] Interactions & Density Focus chain G [auth B] Focus chain H [auth B] Focus chain L [auth A] Focus chain M [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain D [auth B] SDF format, chain E [auth B] SDF format, chain F [auth B] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] MOL2 format, chain D [auth B] MOL2 format, chain E [auth B] MOL2 format, chain F [auth B] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] mmCIF format, chain D [auth B] mmCIF format, chain E [auth B] mmCIF format, chain F [auth B] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A]	D [auth B] E [auth B] F [auth B] I [auth A] J [auth A] D [auth B], E [auth B], F [auth B], I [auth A], J [auth A], K [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain D [auth B] Focus chain E [auth B] Focus chain F [auth B] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Interactions & Density Focus chain D [auth B] Focus chain E [auth B] Focus chain F [auth B] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A]