8I49

Acyl-ACP synthetase structure bound to ATP

Summary for 8I49

• Entry DOI: 10.2210/pdb8i49/pdb
• EMDB information: 35165
• Descriptor: Acyl-acyl carrier protein synthetase, ADENOSINE-5'-TRIPHOSPHATE (2 entities in total)
• Functional Keywords: acyl-acp synthetase, tool enzyme, cytosolic protein
• Biological source: Vibrio harveyi
• Total number of polymer chains: 6
• Total formula weight: 366020.63

Authors

Huang, H.,Wang, C.,Chang, S.,Cui, T.,Xu, Y.,Zhang, H.,Zhou, C.,Zhang, X.,Feng, Y. (deposition date: 2023-01-18, release date: 2024-01-24, Last modification date: 2025-01-22)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.41 Å)