8TKO
KS-AT core of 6-deoxyerythronolide B synthase (DEBS) Module 3 crosslinked with its translocation ACP partner of Module 2
Summary for 8TKO
| Entry DOI | 10.2210/pdb8tko/pdb |
| EMDB information | 41355 |
| Descriptor | EryAII, EryAI (2 entities in total) |
| Functional Keywords | polyketide synthase, antibody, biosynthetic protein |
| Biological source | Saccharopolyspora erythraea More |
| Total number of polymer chains | 3 |
| Total formula weight | 220388.79 |
| Authors | Cogan, D.P.,Soohoo, A.M.,Chen, M.,Brodsky, K.L.,Liu, Y.,Khosla, C. (deposition date: 2023-07-25, release date: 2024-07-31, Last modification date: 2025-06-11) |
| Primary citation | Cogan, D.P.,Soohoo, A.M.,Chen, M.,Liu, Y.,Brodsky, K.L.,Khosla, C. Structural basis for intermodular communication in assembly-line polyketide biosynthesis. Nat.Chem.Biol., 21:876-882, 2025 Cited by PubMed Abstract: Assembly-line polyketide synthases (PKSs) are modular multi-enzyme systems with considerable potential for genetic reprogramming. Understanding how they selectively transport biosynthetic intermediates along a defined sequence of active sites could be harnessed to rationally alter PKS product structures. To investigate functional interactions between PKS catalytic and substrate acyl carrier protein (ACP) domains, we employed a bifunctional reagent to crosslink transient domain-domain interfaces of a prototypical assembly line, the 6-deoxyerythronolide B synthase, and resolved their structures by single-particle cryogenic electron microscopy (cryo-EM). Together with statistical per-particle image analysis of cryo-EM data, we uncovered interactions between ketosynthase (KS) and ACP domains that discriminate between intra-modular and inter-modular communication while reinforcing the relevance of conformational asymmetry during the catalytic cycle. Our findings provide a foundation for the structure-based design of hybrid PKSs comprising biosynthetic modules from different naturally occurring assembly lines. PubMed: 39179672DOI: 10.1038/s41589-024-01709-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.05 Å) |
Structure validation
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