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-Structure paper
タイトル | Priming enzymes from the pikromycin synthase reveal how assembly-line ketosynthases catalyze carbon-carbon chemistry. |
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ジャーナル・号・ページ | Structure, Vol. 30, Issue 9, Page 1331-11339.e3, Year 2022 |
掲載日 | 2022年9月1日 |
著者 | Miles S Dickinson / Takeshi Miyazawa / Ryan S McCool / Adrian T Keatinge-Clay / |
PubMed 要旨 | The first domain of modular polyketide synthases (PKSs) is most commonly a ketosynthase (KS)-like enzyme, KS, that primes polyketide synthesis. Unlike downstream KSs that fuse α-carboxyacyl groups ...The first domain of modular polyketide synthases (PKSs) is most commonly a ketosynthase (KS)-like enzyme, KS, that primes polyketide synthesis. Unlike downstream KSs that fuse α-carboxyacyl groups to growing polyketide chains, it performs an extension-decoupled decarboxylation of these groups to generate primer units. When Pik127, a model triketide synthase constructed from modules of the pikromycin synthase, was studied by cryoelectron microscopy (cryo-EM), the dimeric didomain comprised of KS and the neighboring methylmalonyl-selective acyltransferase (AT) dominated the class averages and yielded structures at 2.5- and 2.8-Å resolution, respectively. Comparisons with ketosynthases complexed with their substrates revealed the conformation of the (2S)-methylmalonyl-S-phosphopantetheinyl portion of KS and KS substrates prior to decarboxylation. Point mutants of Pik127 probed the roles of residues in the KS active site, while an AT-swapped version of Pik127 demonstrated that KS can also decarboxylate malonyl groups. Mechanisms for how KS and KS domains catalyze carbon-carbon chemistry are proposed. |
リンク | Structure / PubMed:35738283 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.61 - 2.86 Å |
構造データ | EMDB-26839, PDB-7uwr: EMDB-27094, PDB-8czc: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | BIOSYNTHETIC PROTEIN / ketosynthase-like / acyltransferase / decarboxylation / methylmalonyl-specific / polyketide synthase |