8HD4

Full-length crystal structure of mycobacterium tuberculosis FadD23 in complex with AMPC16

Summary for 8HD4

• Entry DOI: 10.2210/pdb8hd4/pdb
• Descriptor: Long-chain-fatty-acid--AMP ligase FadD23, palmitoyl adenylate (3 entities in total)
• Functional Keywords: fatty-acid-amp synthetase, biosynthetic protein
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 1
• Total formula weight: 65787.65

Authors

Yan, M.R.,Liu, X.,Zhang, W.,Rao, Z.H. (deposition date: 2022-11-03, release date: 2023-02-15, Last modification date: 2024-05-29)

Primary citation

Yan, M.,Cao, L.,Zhao, L.,Zhou, W.,Liu, X.,Zhang, W.,Rao, Z.
The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms.
Front Microbiol, 14:1090534-1090534, 2023

PubMed Abstract: Sulfolipid-1 (SL-1) is located in the () cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures have not been solved. The crystal structures of FadD23 bound to ATP or hexadecanoyl adenylate was determined in this study. We have also investigated long-chain saturated fatty acids as biological substrates of FadD23 through structural, biological, and chemical analyses. The mutation at the active site of FadD23 greatly influences enzymatic activity. Meanwhile, the FadD23 N-terminal domain alone cannot bind palmitic acid without C-terminal domain facilitation since it is almost inactive after removing the C-terminal domain. FadD23 is the first protein in the SL-1 synthesis pathway whose structure has been solved. These results reveal the importance of the C-terminal domain in the catalytic mechanism.

PubMed: 36896429
DOI: 10.3389/fmicb.2023.1090534

Experimental method

X-RAY DIFFRACTION (2.68 Å)