7JSU

Crystal structure of SARS-CoV-2 3CL protease in complex with GC376

PDB DOI: https://doi.org/10.2210/pdb7JSU/pdb

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

Deposited: 2020-08-16 Released: 2021-03-10
Deposition Author(s): Iketani, S., Forouhar, F., Liu, H., Hong, S.J., Lin, F.-Y., Nair, M.S., Zask, A., Xing, L., Stockwell, B.R., Chavez, A., Ho, D.D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.83 Å
R-Value Free: 0.203
R-Value Work: 0.169
R-Value Observed: 0.173

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors.

Iketani, S., Forouhar, F., Liu, H., Hong, S.J., Lin, F.Y., Nair, M.S., Zask, A., Huang, Y., Xing, L., Stockwell, B.R., Chavez, A., Ho, D.D.

(2021) Nat Commun 12: 2016-2016

PubMed: 33795671 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-021-22362-2
Primary Citation of Related Structures:
7JST, 7JSU, 7JT0, 7JT7, 7JW8

PubMed Abstract:
We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

Organizational Affiliation

Aaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, USA.

Macromolecule Content

Total Structure Weight: 34.42 kDa
Atom Count: 2,560
Modelled Residue Count: 303
Deposited Residue Count: 306
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
3C-like proteinase	A	306	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 0 Gene Names: rep, 1a-1b EC: 3.4.22.69
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 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
UED (Subject of Investigation/LOI) Query on UED Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	N~2~-[(benzyloxy)carbonyl]-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide C₂₁ H₃₁ N₃ O₅ JUCVXDDMQHPCKT-BZSNNMDCSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A]	C [auth A], D [auth A]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain C [auth A] Focus chain D [auth A] Interactions & Density Focus chain C [auth A] Focus chain D [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.83 Å
R-Value Free: 0.203
R-Value Work: 0.169
R-Value Observed: 0.173
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 98.83	α = 90
b = 80.225	β = 114.31
c = 51.99	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
PDB_EXTRACT	data extraction
XDS	data reduction
Aimless	data scaling
MOLREP	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2021-03-10

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2021-03-10
Type: Initial release
Version 1.1: 2021-03-24
Changes: Structure summary
Version 1.2: 2021-04-14
Changes: Database references
Version 1.3: 2024-04-03
Changes: Data collection, Database references, Refinement description, Structure summary
Version 1.4: 2024-11-20
Changes: Structure summary

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.

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