Co-crystal structure of Helicobacter pylori biotin acetyl-CoA carboxylase synthetase (biotin protein ligase) with biotinyl-5-ATP
Jesuferanmi P. Ayanlade, Dylan E. Davis, Sandhya Subramanian, David Dranow, Donald D. Lorimer, Brad Hammerson, Peter J. Myler, and Oluwatoyin A. Asojo [1]
Molecular Tour
Helicobacter pylori, a type 1 carcinogen that causes human gastric ulcers and cancer, is a priority target of the Seattle Structural Genomics Center for Infectious Disease (SSGCID). These efforts include determining the structures of potential H. pylori therapeutic targets. Here, we report the purification, crystallization, and x-ray structure of one such target, H. pylori biotin protein ligase (HpBPL). HpBPL catalyzes the activation of various biotin-dependent metabolic pathways, including fatty acid synthesis, gluconeogenesis, and amino acid catabolism, and may facilitate H. pylori survival in the high pH gastric mucosa. HpBPL is a prototypical bacterial biotin protein ligase despite in the Protein Data Bank via analysis with ENDScript[2][3]. It crystalizes as a . A biotinyl-5-ATP molecule sits in a . HpBPL shares to Mycobacterium tuberculosis biotin protein ligase (MtBPL), despite less than 22% sequence identity. HpBPL’s active site is very similar to MtBPL and has the necessary residues to bind inhibitors developed for MtBPL.
References
- ↑ Ayanlade JP, Davis DE, Subramanian S, Dranow DM, Lorimer DD, Hammerson B, Myler PJ, Asojo OA. Co-crystal structure of Helicobacter pylori biotin protein ligase with biotinyl-5-ATP. Acta Crystallogr F Struct Biol Commun. 2025 Jan 1;81(Pt 1):11-18. PMID:39704719 doi:10.1107/S2053230X24012056
- ↑ Gouet P, Robert X, Courcelle E. ESPript/ENDscript: Extracting and rendering sequence and 3D information from atomic structures of proteins. Nucleic Acids Res. 2003 Jul 1;31(13):3320-3. PMID:12824317
- ↑ Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4. PMID:24753421 doi:10.1093/nar/gku316
