Summary for 8CMS
| Entry DOI | 10.2210/pdb8cms/pdb |
| Descriptor | Ubiquitin thioesterase OTUB2, (1~{S},2~{S})-~{N}'-ethanoyl-2-(3-methylphenyl)cyclopropane-1-carbohydrazide (3 entities in total) |
| Functional Keywords | chemical modification, ubiquitin, deubiquitinase, inhibitor, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 27637.37 |
| Authors | Gan, J.,de Vries, J. (deposition date: 2023-02-21, release date: 2023-11-15, Last modification date: 2024-11-06) |
| Primary citation | Gan, J.,de Vries, J.,Akkermans, J.J.L.L.,Mohammed, Y.,Tjokrodirijo, R.T.N.,de Ru, A.H.,Kim, R.Q.,Vargas, D.A.,Pol, V.,Fasan, R.,van Veelen, P.A.,Neefjes, J.,van Dam, H.,Ovaa, H.,Sapmaz, A.,Geurink, P.P. Cellular Validation of a Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2. Acs Chem.Biol., 18:2003-2013, 2023 Cited by PubMed Abstract: Ubiquitin thioesterase OTUB2, a cysteine protease from the ovarian tumor (OTU) deubiquitinase superfamily, is often overexpressed during tumor progression and metastasis. Development of OTUB2 inhibitors is therefore believed to be therapeutically important, yet potent and selective small-molecule inhibitors targeting OTUB2 are scarce. Here, we describe the development of an improved OTUB2 inhibitor, , comprising a chloroacethydrazide moiety that covalently reacts to the active-site cysteine residue. shows outstanding target engagement and proteome-wide selectivity in living cells. Importantly, as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31. We present a route to future OTUB2-related therapeutics and have shown that the OTUB2 inhibitor developed in this study can help to uncover new aspects of the related biology and open new questions regarding the understanding of OTUB2 regulation at the post-translational modification level. PubMed: 37642399DOI: 10.1021/acschembio.3c00227 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.77 Å) |
Structure validation
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