8IVI

crystal structure of a medium-long chain fatty acyl-CoA ligase

Summary for 8IVI

• Entry DOI: 10.2210/pdb8ivi/pdb
• Descriptor: Medium/long-chain-fatty-acid--CoA ligase FadD8 (1 entity in total)
• Functional Keywords: fatty acyl-coa, ligase, mycobacterial protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 126608.11

Authors

Li, S. (deposition date: 2023-03-27, release date: 2024-02-14)

Primary citation

Li, S.,Qu, Y.
Structural study of medium-long chain fatty acyl-CoA ligase FadD8 from Mycobacterium tuberculosis.
Biochem.Biophys.Res.Commun., 672:65-71, 2023

PubMed Abstract: In mycobacteria, lipids are important components of the cell wall and play a critical role for pathogenic activities. Lipids need to be activated before participating in many biological pathways. FadD proteins are members of the adenylate-forming superfamily, catalyzing activation of fatty acids. FadD8 is one of the 34 Mycobacterium tuberculosis FadD proteins, which was reported to be a putative medium-long chain fatty acyl-CoA ligase. Previous studies showed FadD8 from Mycobacterium smegmatis exhibited higher activity with oxidized cholesterol than fatty acids. However, the catalytic mechanism of the FadD8 is still exclusive. Here, we reported the crystal structure of FadD8 from Mycobacterium tuberculosis, which forms homodimer. Structural analysis revealed presence of a relatively narrow pocket compared to other FadD proteins and a novel alternative pocket, implying distinct substrate binding preference. We propose that FadD8 plays a vital role in cholesterol utilization and metabolism by catalyzing activation of cholesterol. Collectively, our findings provide novel information for the further studies of the inhibitor and drug development.

PubMed: 37336126
DOI: 10.1016/j.bbrc.2023.06.024

Experimental method

X-RAY DIFFRACTION (2.29 Å)