MDM4

From Proteopedia

spinqualitylabelsall models Human MDM4 p53-binding domain (grey) complex with p53 peptide (green) (PDB entry 3dab) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function MDM4 or MDMX is a 490 amino acid protein containing a RING finger domain (residues 300-339) and a nuclear localization signal. MDM4 interacts with protein MDM2[1]. Both of these proteins show structure similarity and contain a p53-binding domain (or SWIB domain) in their N terminal (residues 23-111). Relevance MDM4 which is a negative regulator of p53 is upregulated in human melanomas and thus is a key therapeutic target[2].

3D Structures of MDM4

Updated on 27-June-2023

MDM4 domains: p53-binding 24-111; zinc finger RNBP 290-335; zinc finger-RING 428-490

2cr8 – hMDM4 ZF-RNBP domain – NMR
3dab, 2mwy, 7el4 – hMDM4 p53-binding domain + p53 transactivation domain
3dac – hMDM4 p53-binding domain (mutant) + p53 transactivation domain
2n06, 2n0u, 2n0w, 2n14 – hMDM4 p53-binding domain + p53 transactivation domain – NMR
3fdo, 3jzo, 3jzp, 3jzq, 4rxz, 5uml, 7kjn – hMDM4 p53-binding domain + peptide inhibitor
5vk1 – hMDM4 p53-binding domain + stapled peptide
3lbj, 3u15, 8ia5 – hMDM4 p53-binding domain + inhibitor
3fe7, 3fea, 3eqy - hMDM4 p53-binding domain (mutant) + peptide
6q9q, 6q9s, 6q9u, 6q9w, 6q9y – hMDM4 p53-binding domain (mutant)+ inhibitor
7c3q, 7c3y, 7c44 – hMDM4 p53-binding domain + nutlin
2vyr – hMDM4 p53-binding domain + antibody
2vje, 2vjf – hMDM4 ZF-RING domain + hMDM2 residues 383-446
5mnj – hMDM4 ZF-RING domain + hMDM2 ZF-RING domain + polyubiquitin + ubiquitin-conjugating enzyme E2
7mla – hMDM4 ZF-RING domain + cyclotide - NMR
2z5s - zMDM4 p53-binding domain + p53 transactivation domain – zebrafish
2z5t - zMDM4 p53-binding domain (mutant) + p53 transactivation domain
4n5t, 6v4e, 6v4f, 6v4g, 6v4h - zMDM4 p53-binding domain (mutant) + stapled peptide

References

1. ↑ Migliorini D, Lazzerini Denchi E, Danovi D, Jochemsen A, Capillo M, Gobbi A, Helin K, Pelicci PG, Marine JC. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol Cell Biol. 2002 Aug;22(15):5527-38. PMID:12101245
2. ↑ Gembarska A, Luciani F, Fedele C, Russell EA, Dewaele M, Villar S, Zwolinska A, Haupt S, de Lange J, Yip D, Goydos J, Haigh JJ, Haupt Y, Larue L, Jochemsen A, Shi H, Moriceau G, Lo RS, Ghanem G, Shackleton M, Bernal F, Marine JC. MDM4 is a key therapeutic target in cutaneous melanoma. Nat Med. 2012 Aug;18(8):1239-47. doi: 10.1038/nm.2863. Epub 2012 Jul 22. PMID:22820643 doi:http://dx.doi.org/10.1038/nm.2863