› 8hhu

X-ray diffraction
2.26Å resolution

Crystal structure of the SARS-CoV-2 main protease in complex with SY110

Released:
DOI: 10.2210/pdb8hhu/pdb
PDB entry 8hhu coloured by chain, front view.
PDB entry 8hhu coloured by chain, side view.
PDB entry 8hhu coloured by chain, top view.
Source organism: Severe acute respiratory syndrome coronavirus 2
Primary publication:
A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants.
Huang C, Shuai H, Qiao J, Hou Y, Zeng R, Xia A, Xie L, Fang Z, Li Y, Yoon C, Huang Q, Hu B, You J, Quan B, Zhao X, Guo N, Zhang S, Ma R, Zhang J, Wang Y, Yang R, Zhang S, Nan J, Xu H, Wang F, Lei J, Chu H, Yang S
OpenAccess logo Signal Transduct Target Ther 8 128 (2023)
PMID: 36928316

Function and Biology Details

Reactions catalysed: 
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-144140 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3C-like proteinase nsp5 Chain: A
Molecule details ›
Chain: A
Length: 306 amino acids
Theoretical weight: 33.87 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Escherichia coli
UniProt:
  • Canonical: P0DTC1 (Residues: 3264-3569; Coverage: 7%)
Sequence domains: Coronavirus endopeptidase C30

Ligands and Environments

1 bound ligand:
Ligand LVX 1 x LVX
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: MAX IV BEAMLINE BioMAX
Spacegroup: C2
Unit cell:
a: 98.704Å b: 82.411Å c: 51.946Å
α: 90° β: 114.69° γ: 90°
R-values:
R R work R free
0.187 0.185 0.227
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China.
Wei et al. (2023)
1 more

2 mentions without citation

Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives.
Citarella et al. (2023)
1 more