+検索条件
-Structure paper
タイトル | Structural basis for intermodular communication in assembly-line polyketide biosynthesis. |
---|---|
ジャーナル・号・ページ | Nat Chem Biol, Year 2024 |
掲載日 | 2024年8月23日 |
著者 | Dillon P Cogan / Alexander M Soohoo / Muyuan Chen / Yan Liu / Krystal L Brodsky / Chaitan Khosla / |
PubMed 要旨 | Assembly-line polyketide synthases (PKSs) are modular multi-enzyme systems with considerable potential for genetic reprogramming. Understanding how they selectively transport biosynthetic ...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. |
リンク | Nat Chem Biol / PubMed:39179672 |
手法 | EM (単粒子) |
解像度 | 3.05 - 3.73 Å |
構造データ | EMDB-41305, PDB-8tjn: EMDB-41306, PDB-8tjo: EMDB-41307, PDB-8tjp: EMDB-41355, PDB-8tko: EMDB-41495, PDB-8tpw: EMDB-41496, PDB-8tpx: |
由来 |
|
キーワード | BIOSYNTHETIC PROTEIN/IMMUNE SYSTEM / polyketide synthase / antibody / BIOSYNTHETIC PROTEIN-IMMUNE SYSTEM complex / BIOSYNTHETIC PROTEIN |