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5ufi

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DCN1 bound to DI-591

Structural highlights

5ufi is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	DCUN1D1, DCUN1L1, RP42, SCCRO (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DCNL1_HUMAN] Part of an E3 ubiquitin ligase complex for neddylation. Required for neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes by enhancing the rate of cullins neddylation. Functions to recruit the NEDD8-charged E2 enzyme to the cullin component. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity. Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity).

Publication Abstract from PubMed

The Cullin-RING E3 ubiquitin ligases (CRLs) regulate homeostasis of ~20% of cellular proteins and their activation require neddylation of their cullin subunit. Cullin neddylation is modulated by a scaffolding DCN protein through interactions with both the cullin protein and an E2 enzyme such as UBC12. Here we report the development of DI-591 as a high-affinity, cell-permeable small-molecule inhibitor of the DCN1-UBC12 interaction. DI-591 binds to purified recombinant human DCN1 and DCN2 proteins with K i values of 10-12 nM, and disrupts the DCN1-UBC12 interaction in cells. Treatment with DI-591 selectively converts cellular cullin 3 into an un-neddylated inactive form with no or minimum effect on other cullin members. Our data firmly establish a previously unrecognized specific role of the DCN1-UBC12 interaction for cellular neddylation of cullin 3. DI-591 is an excellent probe compound to investigate the role of the cullin 3 CRL ligase in biological processes and human diseases.

A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation.,Zhou H, Lu J, Liu L, Bernard D, Yang CY, Fernandez-Salas E, Chinnaswamy K, Layton S, Stuckey J, Yu Q, Zhou W, Pan Z, Sun Y, Wang S Nat Commun. 2017 Oct 27;8(1):1150. doi: 10.1038/s41467-017-01243-7. PMID:29074978^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhou H, Lu J, Liu L, Bernard D, Yang CY, Fernandez-Salas E, Chinnaswamy K, Layton S, Stuckey J, Yu Q, Zhou W, Pan Z, Sun Y, Wang S. A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation. Nat Commun. 2017 Oct 27;8(1):1150. doi: 10.1038/s41467-017-01243-7. PMID:29074978 doi:http://dx.doi.org/10.1038/s41467-017-01243-7