8I6M

Acyl-ACP synthetase structure bound to AMP-C18:1

8I6M の概要

• エントリーDOI: 10.2210/pdb8i6m/pdb
• EMDBエントリー: 35200
• 分子名称: Acyl-acyl carrier protein synthetase, OLEIC ACID, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: acyl-acp synthetase, tool enzyme, cytosolic protein, transferase
• 由来する生物種: Vibrio harveyi
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 366901.47

構造登録者

Huang, H.,Wang, C.,Chang, S.,Cui, T.,Xu, Y.,Zhang, H.,Zhou, C.,Zhang, X.,Feng, Y. (登録日: 2023-01-28, 公開日: 2024-01-31, 最終更新日: 2025-01-22)

主引用文献

Huang, H.,Wang, C.,Chang, S.,Cui, T.,Xu, Y.,Huang, M.,Zhang, H.,Zhou, C.,Zhang, X.,Feng, Y.
Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Fatty acids (FAs) are essential building blocks for all the domains of life, of which bacterial de novo synthesis, called type II FA synthesis (FAS II), is energetically expensive. The recycling of exogenous FAs (eFAs) partially relieves the FAS II demand and, therefore, compromises the efficacy of FAS II-directed antimicrobials. The versatile acyl-acyl carrier protein (ACP) synthetase, AasS, enables bacterial channeling of diverse eFA nutrients through holo-ACP, an activated form of ACP. However, the molecular mechanism for AasS catalysis is not fully understood. Here we report a series of cryo-electron microscopy structures of AasS from the bioluminescent bacterium Vibrio harveyi to provide insights into the catalytic cycle. AasS forms a ring-shaped hexamer, with each protomer folding into two distinct domains. Biochemical and structural analysis suggests that AasS accommodates distinct eFA substrates and the conserved W230 residue has a gating role. Adenosine triphosphate and Mg binding converts the AasS hexamer to a tetramer, which is likely needed for the acyl adenylate intermediate formation. Afterward, AasS reverts to the hexamer conformation in adaption to acyl-ACP production. The complete landscape for eFA scavenging lays a foundation for exploiting the versatility of AasS in biopharmaceuticals.

PubMed: 39794554
DOI: 10.1038/s41594-024-01464-7

実験手法

ELECTRON MICROSCOPY (2.59 Å)