5F6V: Crystal Structure Of Ubc9 (k48/k49a/e54a) Complexed With Fragment 1 (biphenol From Fragment Cocktail Screen)

Citation:
Abstract
Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is an important disease-associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray crystallographic screen was used to identify two distinct small-molecule fragments that bind to Ubc9 at a site distal to its catalytic cysteine. These fragments and related compounds inhibit SUMO conjugation in biochemical assays with potencies of 1.9-5.8 mm. Mechanistic and biophysical analyses, coupled with molecular dynamics simulations, point toward ligand-induced rigidification of Ubc9 as a mechanism of inhibition.
PDB ID: 5F6VDownload
MMDB ID: 138558
PDB Deposition Date: 2015/12/7
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 1.49  Å
Source Organism:
Similar Structures:
Biological Unit for 5F6V: monomeric; determined by author and by software (PISA)
Molecular Components in 5F6V
Label Count Molecule
Protein (1 molecule)
1
Sumo-conjugating Enzyme Ubc9(Gene symbol: UBE2I)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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