› 1mhw

X-ray diffraction
1.9Å resolution

Design of non-covalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides

Released:
DOI: 10.2210/pdb1mhw/pdb
PDB entry 1mhw coloured by chain, front view.
PDB entry 1mhw coloured by chain, side view.
PDB entry 1mhw coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides.
Chowdhury SF, Sivaraman J, Wang J, Devanathan G, Lachance P, Qi H, Ménard R, Lefebvre J, Konishi Y, Cygler M, Sulea T, Purisima EO
J Med Chem 45 5321-9 (2002)
PMID: 12431059

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 domain:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-139720 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Cathepsin L heavy chain Chains: A, B
Molecule details ›
Chains: A, B
Length: 175 amino acids
Theoretical weight: 19.13 KDa
Source organism: Homo sapiens
Expression system: Komagataella pastoris
UniProt:
  • Canonical: P07711 (Residues: 114-288; Coverage: 55%)
Gene names: CTSL, CTSL1
Sequence domains: Papain family cysteine protease
Structure domains: Cysteine proteinases
Cathepsin L light chain Chains: C, D
Molecule details ›
Chains: C, D
Length: 42 amino acids
Theoretical weight: 4.78 KDa
Source organism: Homo sapiens
Expression system: Komagataella pastoris
UniProt:
  • Canonical: P07711 (Residues: 292-333; Coverage: 13%)
Gene names: CTSL, CTSL1
Structure domains: Cysteine proteinases. Chain C
4-biphenylacetyl-Cys-(D)Arg-Tyr-N-(2-phenylethyl) amide Chains: E, F, G, H
Molecule details ›
Chains: E, F, G, H
Length: 5 amino acids
Theoretical weight: 740 Da

Ligands and Environments

No bound ligands
2 modified residues:
Ligand CSD 2 x CSD
Ligand DAR 4 x DAR

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU300
Spacegroup: P212121
Unit cell:
a: 51.522Å b: 58.632Å c: 151.445Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.185 0.185 0.23
Expression system: Komagataella pastoris

Quick links

Citations

3 review citations

Biochemical properties and regulation of cathepsin K activity.
Lecaille et al. (2008)
2 more

15 mentions without citation

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