8x8j

From Proteopedia

The structure of AbBioc in complex with inhibitor sinefungin

Structural highlights

8x8j is a 2 chain structure with sequence from Acinetobacter baumannii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.72Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A1E3M3A7_ACIBA Converts the free carboxyl group of a malonyl-thioester to its methyl ester by transfer of a methyl group from S-adenosyl-L-methionine (SAM). It allows to synthesize pimeloyl-ACP via the fatty acid synthetic pathway.[HAMAP-Rule:MF_00835]

Publication Abstract from PubMed

The covalently attached cofactor biotin plays pivotal roles in central metabolism. The top-priority ESKAPE-type pathogens, Acinetobacter baumannii and Klebsiella pneumoniae, 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 A. baumannii and KpBioC for K. pneumoniae) 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 bioC rendered A. baumannii and K. pneumoniae 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 K. pneumoniae infection and A. baumannii colistin resistance.

A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway.,Su Z, Zhang W, Shi Y, Cui T, Xu Y, Yang R, Huang M, Zhou C, Zhang H, Lu T, Qu J, He ZG, Gan J, Feng Y Sci Adv. 2024 Dec 20;10(51):eadp3954. doi: 10.1126/sciadv.adp3954. Epub 2024 Dec , 20. PMID:39705367^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Su Z, Zhang W, Shi Y, Cui T, Xu Y, Yang R, Huang M, Zhou C, Zhang H, Lu T, Qu J, He ZG, Gan J, Feng Y. A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway. Sci Adv. 2024 Dec 20;10(51):eadp3954. PMID:39705367 doi:10.1126/sciadv.adp3954