7M02

Structure of SARS-CoV-2 3CL protease in complex with inhibitor 17c

PDB DOI: https://doi.org/10.2210/pdb7M02/pdb

Classification: HYDROLASE/INHIBITOR
Organism(s): Severe acute respiratory syndrome coronavirus 2
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2021-03-10 Released: 2021-03-24
Deposition Author(s): Lovell, S., Kashipathy, M.M., Battaile, K.P., Chamandi, S.D., Rathnayake, A.D., Kim, Y., Perera, K.D., Jesri, A.R.M., Nguyen, H.N., Baird, M.A., Miller, M.J., Groutas, W.C., Chang, K.O.
Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.241
R-Value Work: 0.181
R-Value Observed: 0.184

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

Structure-Guided Design of Potent Inhibitors of SARS-CoV-2 3CL Protease: Structural, Biochemical, and Cell-Based Studies.

Dampalla, C.S., Rathnayake, A.D., Perera, K.D., Jesri, A.M., Nguyen, H.N., Miller, M.J., Thurman, H.A., Zheng, J., Kashipathy, M.M., Battaile, K.P., Lovell, S., Perlman, S., Kim, Y., Groutas, W.C., Chang, K.O.

(2021) J Med Chem 64: 17846-17865

PubMed: 34865476 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/acs.jmedchem.1c01037
Primary Citation of Related Structures:
7LZT, 7LZU, 7LZV, 7LZW, 7LZX, 7LZY, 7LZZ, 7M00, 7M01, 7M02, 7M03, 7M04

PubMed Abstract:
The COVID-19 pandemic is having a major impact on public health worldwide, and there is an urgent need for the creation of an armamentarium of effective therapeutics, including vaccines, biologics, and small-molecule therapeutics, to combat SARS-CoV-2 and emerging variants. Inspection of the virus life cycle reveals multiple viral- and host-based choke points that can be exploited to combat the virus. SARS-CoV-2 3C-like protease (3CLpro), an enzyme essential for viral replication, is an attractive target for therapeutic intervention, and the design of inhibitors of the protease may lead to the emergence of effective SARS-CoV-2-specific antivirals. We describe herein the results of our studies related to the application of X-ray crystallography, the Thorpe-Ingold effect, deuteration, and stereochemistry in the design of highly potent and nontoxic inhibitors of SARS-CoV-2 3CLpro.

Organizational Affiliation

Department of Chemistry, Wichita State University, Wichita, Kansas 67260, United States.

Macromolecule Content

Total Structure Weight: 70.34 kDa
Atom Count: 4,772
Modelled Residue Count: 595
Deposited Residue Count: 618
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
3C-like proteinase	A, B	309	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 Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
YL7 Query on YL7 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain E [auth B] MOL2 format, chain C [auth A] MOL2 format, chain E [auth B] mmCIF format, chain C [auth A] mmCIF format, chain E [auth B]	C [auth A], E [auth B]	(1S,2S)-2-((S)-2-((((2-fluorobenzyl)oxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((R)-2-oxo-3,4-dihydro-2H-pyrrol-3-yl)propane-1-sulfonic acid C₂₁ H₂₈ F N₃ O₈ S VAWJCTITNJHIPN-FDRFZEDHSA-N		Interactions Focus chain C [auth A] Focus chain E [auth B] Interactions & Density Focus chain C [auth A] Focus chain E [auth B]
YKY Query on YKY Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain F [auth B] MOL2 format, chain D [auth A] MOL2 format, chain F [auth B] mmCIF format, chain D [auth A] mmCIF format, chain F [auth B]	D [auth A], F [auth B]	(1R,2S)-2-((S)-2-((((2-fluorobenzyl)oxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((R)-2-oxo-3,4-dihydro-2H-pyrrol-3-yl)propane-1-sulfonic acid C₂₁ H₂₈ F N₃ O₈ S VAWJCTITNJHIPN-VZYKRBATSA-N		Interactions Focus chain D [auth A] Focus chain F [auth B] Interactions & Density Focus chain D [auth A] Focus chain F [auth B]
PG4 Query on PG4 Download Ideal Coordinates CCD File SDF format, chain G [auth B] MOL2 format, chain G [auth B] mmCIF format, chain G [auth B]	G [auth B]	TETRAETHYLENE GLYCOL C₈ H₁₈ O₅ UWHCKJMYHZGTIT-UHFFFAOYSA-N		Interactions Focus chain G [auth B] Interactions & Density Focus chain G [auth B]