9CQ1

Condensing region of EcPKS1

9CQ1 の概要

• エントリーDOI: 10.2210/pdb9cq1/pdb
• EMDBエントリー: 45806 45806
• 分子名称: EcPKS1 - condensing region (1 entity in total)
• 機能のキーワード: polyketide adenosyl transferase, beta-keto-synthase, dehydratase, keto-redctase, acyl carrier protein, biosynthetic protein
• 由来する生物種: Elysia chlorotica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 498647.97

構造登録者

Schubert, H.L.,Hill, C.P. (登録日: 2024-07-19, 公開日: 2025-01-29, 最終更新日: 2025-02-19)

主引用文献

Schubert, H.L.,Li, F.,Hill, C.P.,Schmidt, E.W.
The structure of full-length AFPK supports the ACP linker in a role that regulates iterative polyketide and fatty acid assembly.
Proc.Natl.Acad.Sci.USA, 122:e2419884122-e2419884122, 2025

PubMed Abstract: The polyketide synthases (PKSs) in microbes and the cytoplasmic fatty acid synthases in humans (FASs) are related enzymes that have been well studied. As a result, there is a paradigm explaining in general terms how FASs repeatedly use a set of enzymatic domains to produce simple fats, while PKSs use the domains in a much more complex manner to produce pharmaceuticals and other elaborate molecules. However, most animals also have PKSs that do not conform to the rules described in microbes, including a large family of enzymes that bridge fatty acid and polyketide metabolism, the animal FAS-like PKSs (AFPKs). Here, we present the cryoelectron microscopy structures of two AFPKs from sea slugs. While the AFPK resemble mammalian FASs, their chemical products mimic those of PKSs in complexity. How then does the architecture of AFPKs facilitate this structural complexity? Unexpectedly, chemical complexity is controlled not solely by the enzymatic domains but is aided by the dynamics of the acyl carrier protein (ACP), a shuttle that moves intermediates between these domains. We observed interactions between enzyme domains and the linker-ACP domain, which, when manipulated, altered the kinetic properties of the enzyme to change the resulting chemical products. This unveils elaborate mechanisms and enzyme motions underlying lipid and polyketide biochemistry across the domains of life.

PubMed: 39913209
DOI: 10.1073/pnas.2419884122

実験手法

ELECTRON MICROSCOPY (4.3 Å)