4QLQ
yCP in complex with tripeptidic epoxyketone inhibitor 8
Summary for 4QLQ
| Entry DOI | 10.2210/pdb4qlq/pdb |
| Related | 1G65 1RYP 4QLS 4QLT 4QLU 4QLV |
| Descriptor | Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (18 entities in total) |
| Functional Keywords | proteasome, epoxyketone, immunoproteasome inhibitor, binding analysis, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Saccharomyces cerevisiae (Baker's yeast) More |
| Cellular location | Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451 |
| Total number of polymer chains | 28 |
| Total formula weight | 734381.10 |
| Authors | De Bruin, G.,Huber, E.,Xin, B.,Van Rooden, E.,Al-Ayed, K.,Kim, K.,Kisselev, A.,Driessen, C.,Van der Marel, G.,Groll, M.,Overkleeft, H. (deposition date: 2014-06-13, release date: 2014-07-23, Last modification date: 2023-11-08) |
| Primary citation | De Bruin, G.,Huber, E.M.,Xin, B.T.,Van Rooden, E.J.,Al-Ayed, K.,Kim, K.B.,Kisselev, A.F.,Driessen, C.,Van der Stelt, M.,Van der Marel, G.A.,Groll, M.,Overkleeft, H.S. Structure-based design of beta 1i or beta 5i specific inhibitors of human immunoproteasomes J.Med.Chem., 57:6197-6209, 2014 Cited by PubMed Abstract: Mammalian genomes encode seven catalytic proteasome subunits, namely, β1c, β2c, β5c (assembled into constitutive 20S proteasome core particles), β1i, β2i, β5i (incorporated into immunoproteasomes), and the thymoproteasome-specific subunit β5t. Extensive research in the past decades has yielded numerous potent proteasome inhibitors including compounds currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. Proteasome inhibitors that selectively target combinations of β1c/β1i, β2c/β2i, or β5c/β5i are available, yet ligands truly selective for a single proteasome activity are scarce. In this work we report the development of cell-permeable β1i and β5i selective inhibitors that outperform existing leads in terms of selectivity and/or potency. These compounds are the result of a rational design strategy using known inhibitors as starting points and introducing structural features according to the X-ray structures of the murine constitutive and immunoproteasome 20S core particles. PubMed: 25006746DOI: 10.1021/jm500716s PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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