› 6f06

X-ray diffraction
2.02Å resolution

CATHEPSIN L IN COMPLEX WITH (3S,14E)-8-(azetidin-3-yl)-19-chloro-N-(1-cyanocyclopropyl)-5-oxo-12,17-dioxa-4-azatricyclo[16.2.2.06,11]docosa-1(21),6,8,10,14,18(22),19-heptaene-3-carboxamide

Released:
DOI: 10.2210/pdb6f06/pdb
PDB entry 6f06 coloured by chain, front view.
PDB entry 6f06 coloured by chain, side view.
PDB entry 6f06 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.
Giroud M, Dietzel U, Anselm L, Banner D, Kuglstatter A, Benz J, Blanc JB, Gaufreteau D, Liu H, Lin X, Stich A, Kuhn B, Schuler F, Kaiser M, Brun R, Schirmeister T, Kisker C, Diederich F, Haap W
J Med Chem 61 3350-3369 (2018)
PMID: 29590750

Function and Biology Details

Reaction catalysed: 
Similar to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-139718 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cathepsin L Chains: A, B
Molecule details ›
Chains: A, B
Length: 220 amino acids
Theoretical weight: 24.19 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P07711 (Residues: 114-333; Coverage: 70%)
Gene names: CTSL, CTSL1
Sequence domains: Papain family cysteine protease
Structure domains: Cysteine proteinases

Ligands and Environments

3 bound ligands:
Ligand C7T 2 x C7T
Ligand ZN 14 x ZN
Ligand CL 2 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 43.04Å b: 50.791Å c: 84.911Å
α: 90° β: 91.53° γ: 90°
R-values:
R R work R free
0.205 0.201 0.274
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Covalent Inhibitors for Neglected Diseases: An Exploration of Novel Therapeutic Options.
Alves et al. (2023)
7 other articles

4 mentions without citation

A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L.
Dana et al. (2020)
3 more