› 9atf

X-ray diffraction
1.5Å resolution

Crystal structure of MERS 3CL protease in complex with a 1-methyl-4,4-difluorocyclohexyl 2-pyrrolidone inhibitor

Released:
DOI: 10.2210/pdb9atf/pdb
PDB entry 9atf coloured by chain, front view.
PDB entry 9atf coloured by chain, side view.
PDB entry 9atf coloured by chain, top view.
Source organism: Middle East respiratory syndrome-related coronavirus
Primary publication:
Structure-Guided Design of Potent Coronavirus Inhibitors with a 2-Pyrrolidone Scaffold: Biochemical, Crystallographic, and Virological Studies.
Dampalla CS, Kim Y, Zabiegala A, Howard DJ, Nguyen HN, Madden TK, Thurman HA, Cooper A, Liu L, Battaile KP, Lovell S, Chang KO, Groutas WC
J Med Chem (2024)
PMID: 38953866

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:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-125698 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3C-like proteinase nsp5 Chain: A
Molecule details ›
Chain: A
Length: 313 amino acids
Theoretical weight: 34.31 KDa
Source organism: Middle East respiratory syndrome-related coronavirus
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: K9N638 (Residues: 3248-3553; Coverage: 7%)
Gene name: 1a
Sequence domains: Coronavirus endopeptidase C30

Ligands and Environments

2 bound ligands:
Ligand A1AGP 1 x A1AGP
Ligand A1AGO 1 x A1AGO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS-II BEAMLINE 19-ID
Spacegroup: C2
Unit cell:
a: 101.125Å b: 58.034Å c: 49.97Å
α: 90° β: 112.51° γ: 90°
R-values:
R R work R free
0.156 0.155 0.179
Expression system: Escherichia coli BL21(DE3)

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