8X8J

The structure of AbBioc in complex with inhibitor sinefungin

Summary for 8X8J

• Entry DOI: 10.2210/pdb8x8j/pdb
• Descriptor: Malonyl-[acyl-carrier protein] O-methyltransferase, SINEFUNGIN, GLYCEROL, ... (6 entities in total)
• Functional Keywords: bioc methyltransferase, druggable pathway, biotin synthesis, transferase
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 59168.91

Authors

Zhang, W.Z.,Gan, J.,Feng, Y.J. (deposition date: 2023-11-27, release date: 2024-11-13, Last modification date: 2025-04-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.72 Å)