8X8J

The structure of AbBioc in complex with inhibitor sinefungin

8X8J の概要

• エントリーDOI: 10.2210/pdb8x8j/pdb
• 分子名称: Malonyl-[acyl-carrier protein] O-methyltransferase, SINEFUNGIN, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: bioc methyltransferase, druggable pathway, biotin synthesis, transferase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59168.91

構造登録者

Zhang, W.Z.,Gan, J.,Feng, Y.J. (登録日: 2023-11-27, 公開日: 2024-11-13, 最終更新日: 2025-04-23)

主引用文献

Su, Z.,Zhang, W.,Shi, Y.,Cui, T.,Xu, Y.,Yang, R.,Huang, M.,Zhou, C.,Zhang, H.,Lu, T.,Qu, J.,He, Z.G.,Gan, J.,Feng, Y.
A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway.
Sci Adv, 10:eadp3954-eadp3954, 2024

PubMed Abstract: The covalently attached cofactor biotin plays pivotal roles in central metabolism. The top-priority ESKAPE-type pathogens, and , constitute a public health challenge of global concern. Despite the fact that the late step of biotin synthesis is a validated anti-ESKAPE drug target, the primary stage remains fragmentarily understood. We report the functional definition of two BioC isoenzymes (AbBioC for and KpBioC for ) that act as malonyl-ACP methyltransferase and initiate biotin synthesis. The physiological requirement of biotin is diverse within ESKAPE pathogens. CRISPR-Cas9-based inactivation of rendered and biotin auxotrophic. The availability of soluble AbBioC enabled the in vitro reconstitution of DTB/biotin synthesis. We solved two crystal structures of AbBioC bound to SAM cofactor (2.54 angstroms) and sinefungin (SIN) inhibitor (1.72 angstroms). Structural and functional study provided molecular basis for SIN inhibition of BioC. We demonstrated that BioC methyltransferase plays dual roles in infection and colistin resistance.

PubMed: 39705367
DOI: 10.1126/sciadv.adp3954

実験手法

X-RAY DIFFRACTION (1.72 Å)