8BW1
Yeast 20S proteasome in complex with an engineered fellutamide derivative (C14QAL)
Summary for 8BW1
| Entry DOI | 10.2210/pdb8bw1/pdb |
| Related | 3D29 |
| Descriptor | Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (19 entities in total) |
| Functional Keywords | hydrolase-hydrolase inhibitor complex, proteasome, semisynthesis, inhibitor, binding analysis, hydrolase |
| Biological source | Saccharomyces cerevisiae (baker's yeast) More |
| Total number of polymer chains | 32 |
| Total formula weight | 733530.64 |
| Authors | Bozhueyuek, K.A.J.,Praeve, L.,Kegler, C.,Kaiser, S.,Shi, Y.,Kuttenlochner, W.,Schenk, L.,Groll, M.,Hochberg, G.K.A.,Bode, H.B. (deposition date: 2022-12-06, release date: 2023-12-20, Last modification date: 2024-04-03) |
| Primary citation | Bozhuyuk, K.A.J.,Prave, L.,Kegler, C.,Schenk, L.,Kaiser, S.,Schelhas, C.,Shi, Y.N.,Kuttenlochner, W.,Schreiber, M.,Kandler, J.,Alanjary, M.,Mohiuddin, T.M.,Groll, M.,Hochberg, G.K.A.,Bode, H.B. Evolution-inspired engineering of nonribosomal peptide synthetases. Science, 383:eadg4320-eadg4320, 2024 Cited by PubMed Abstract: Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired "eXchange Unit between T domains" (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments. PubMed: 38513038DOI: 10.1126/science.adg4320 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.25 Å) |
Structure validation
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