› 7alh

X-ray diffraction
1.65Å resolution

Crystal structure of the main protease (3CLpro/Mpro) of SARS-CoV-2 at 1.65A resolution (spacegroup C2).

Released:
DOI: 10.2210/pdb7alh/pdb
PDB entry 7alh coloured by chain, front view.
PDB entry 7alh coloured by chain, side view.
PDB entry 7alh coloured by chain, top view.
Source organism: Severe acute respiratory syndrome coronavirus 2
Primary publication:
Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L.
Costanzi E, Kuzikov M, Esposito F, Albani S, Demitri N, Giabbai B, Camasta M, Tramontano E, Rossetti G, Zaliani A, Storici P
OpenAccess logo Int J Mol Sci 22 (2021)
PMID: 34769210

Function and Biology Details

Reactions catalysed: 
S-adenosyl-L-methionine + a 5'-(5'-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA]
S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
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.
ATP + H(2)O = ADP + phosphate
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-145080 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3C-like proteinase nsp5 Chain: A
Molecule details ›
Chain: A
Length: 306 amino acids
Theoretical weight: 33.83 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Escherichia coli
UniProt:
  • Canonical: P0DTD1 (Residues: 3264-3569; Coverage: 4%)
Gene names: 1a-1b, rep
Sequence domains: Coronavirus endopeptidase C30

Ligands and Environments

No bound ligands
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ELETTRA BEAMLINE 11.2C
Spacegroup: C2
Unit cell:
a: 115.218Å b: 54.183Å c: 44.78Å
α: 90° β: 101.176° γ: 90°
R-values:
R R work R free
0.166 0.165 0.189
Expression system: Escherichia coli

Quick links

Citations

6 review citations

The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19.
Hu et al. (2022)
5 more

8 mentions without citation

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