› 5c91

X-ray diffraction
2.44Å resolution

NEDD4 HECT with covalently bound indole-based inhibitor

Released:
DOI: 10.2210/pdb5c91/pdb
PDB entry 5c91 coloured by chain, front view.
PDB entry 5c91 coloured by chain, side view.
PDB entry 5c91 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A Small Molecule That Switches a Ubiquitin Ligase From a Processive to a Distributive Enzymatic Mechanism.
Kathman SG, Span I, Smith AT, Xu Z, Zhan J, Rosenzweig AC, Statsyuk AV
J Am Chem Soc 137 12442-5 (2015)
PMID: 26371805

Function and Biology Details

Reaction catalysed: 
(1a) S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [HECT-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-155546 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
E3 ubiquitin-protein ligase NEDD4 Chain: A
Molecule details ›
Chain: A
Length: 375 amino acids
Theoretical weight: 44.74 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P46934 (Residues: 938-1312; Coverage: 28%)
Gene names: KIAA0093, NEDD4, NEDD4-1, PIG53, RPF1
Sequence domains: HECT-domain (ubiquitin-transferase)

Ligands and Environments

1 bound ligand:
Ligand 4YU 1 x 4YU
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 23-ID-D
Spacegroup: C2
Unit cell:
a: 175.2Å b: 38.73Å c: 60.36Å
α: 90° β: 93.13° γ: 90°
R-values:
R R work R free
0.25 0.248 0.298
Expression system: Escherichia coli

Quick links

Citations

17 review citations

Regulating the human HECT E3 ligases.
Sluimer et al. (2018)
16 more

9 mentions without citation

Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities.
Chen et al. (2018)
8 more