› 5wkl

X-ray diffraction
1.85Å resolution

1.85 A resolution structure of MERS 3CL protease in complex with piperidine-based peptidomimetic inhibitor 17

Released:
DOI: 10.2210/pdb5wkl/pdb
PDB entry 5wkl coloured by chain, front view.
PDB entry 5wkl coloured by chain, side view.
PDB entry 5wkl coloured by chain, top view.
Source organism: Middle East respiratory syndrome-related coronavirus
Primary publication:
Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element.
Galasiti Kankanamalage AC, Kim Y, Damalanka VC, Rathnayake AD, Fehr AR, Mehzabeen N, Battaile KP, Lovell S, Lushington GH, Perlman S, Chang KO, Groutas WC
Eur J Med Chem 150 334-346 (2018)
PMID: 29544147

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-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
UniProt:
  • Canonical: K9N638 (Residues: 3248-3553; Coverage: 7%)
Gene name: 1a
Sequence domains: Coronavirus endopeptidase C30
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand AVY 1 x AVY
Ligand B3J 1 x B3J
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2
Unit cell:
a: 101.253Å b: 58.099Å c: 49.734Å
α: 90° β: 112° γ: 90°
R-values:
R R work R free
0.166 0.163 0.212
Expression system: Escherichia coli BL21

Quick links

Citations

17 review citations

Recent discovery and development of inhibitors targeting coronaviruses.
Pillaiyar et al. (2020)
16 more

5 mentions without citation

What coronavirus 3C-like protease tells us: From structure, substrate selectivity, to inhibitor design.
Xiong et al. (2021)
4 more