8IQU

Structure of MtbFadD23 with PhU-AMS

8IQU の概要

• エントリーDOI: 10.2210/pdb8iqu/pdb
• 分子名称: Fatty-acid-CoA ligase FadD23, 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine (3 entities in total)
• 機能のキーワード: long-chain-fatty-acid-amp ligase, ligase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 65808.71

構造登録者

Yan, M.R.,Zhang, W. (登録日: 2023-03-17, 公開日: 2023-04-26, 最終更新日: 2023-08-23)

主引用文献

Yan, M.,Ma, M.,Chen, R.,Cao, Y.,Zhang, W.,Liu, X.
Structural basis for the development of potential inhibitors targeting FadD23 from Mycobacterium tuberculosis.
Acta Crystallogr.,Sect.F, 79:208-216, 2023

PubMed Abstract: Sulfolipid-1 (SL-1) is a lipid that is abundantly found in the cell wall of Mycobacterium tuberculosis (Mtb). MtbFadD23 is crucial in the SL-1 synthesis pathway. Previously, 5'-O-[N-(11-phenoxyundecanoyl)sulfamoyl]adenosine (PhU-AMS) has been shown to be a general inhibitor of fatty-acid-adenylating enzymes (FadDs) in Mtb. However, the fatty acyl-AMP ligase (FAAL) class of FadDs, which includes MtbFadD23, appears to be functionally nonredundant in the production of multiple fatty acids. In this study, the ability of PhU-AMS to bind to MtbFadD23 was examined under in vitro conditions. The crystal structure of the MtbFadD23-PhU-AMS complex was determined at a resolution of 2.64 Å. Novel features were identified by structural analysis and comparison. Although PhU-AMS could bind to MtbFadD23, it did not inhibit the FAAL adenylation activity of MtbFadD23. However, PhU-AMS improved the main T value in a differential scanning fluorimetry assay, and a structural comparison of MtbFadD23-PhU-AMS with FadD32 and PA1221 suggested that PhU-AMS blocks the loading of the acyl chain onto Pks2. This study sheds light on the structure-based design of specific inhibitors of MtbFadD23 and general inhibitors of FAALs.

PubMed: 37522751
DOI: 10.1107/S2053230X23005836

実験手法

X-RAY DIFFRACTION (2.64 Å)