6CK0

Crystal Structure of Biotin Acetyl Coenzyme A Carboxylase Synthetase from Helicobacter pylori with bound Biotinylated ATP

Summary for 6CK0

• Entry DOI: 10.2210/pdb6ck0/pdb
• Descriptor: Biotin acetyl coenzyme A carboxylase synthetase, 5'-O-[(S)-({5-[(2R,3aS,4S,6aR)-2-hydroxyhexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl}oxy){[(S)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]adenosine, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ssgcid, biotin-[acetyl-coa-carboxylase] ligase activity, structural genomics, seattle structural genomics center for infectious disease, ligase
• Biological source: Helicobacter pylori (strain G27)
• Total number of polymer chains: 2
• Total formula weight: 52133.27

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2018-02-27, release date: 2018-04-04, Last modification date: 2025-01-15)

Primary citation

Ayanlade, J.P.,Davis, D.E.,Subramanian, S.,Dranow, D.M.,Lorimer, D.D.,Hammerson, B.,Myler, P.J.,Asojo, O.A.
Co-crystal structure of Helicobacter pylori biotin protein ligase with biotinyl-5-ATP.
Acta Crystallogr.,Sect.F, 81:11-18, 2025

PubMed Abstract: 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, the purification, crystallization and X-ray structure of one such target, H. pylori biotin protein ligase (HpBPL), are reported. HpBPL catalyzes the activation of various biotin-dependent metabolic pathways, including fatty-acid synthesis, gluconeogenesis and amino-acid catabolism, and may facilitate the survival of H. pylori in the high-pH gastric mucosa. HpBPL is a prototypical bacterial biotin protein ligase, despite having less than 35% sequence identity to any reported structure in the Protein Data Bank. A biotinyl-5-ATP molecule sits in a well conserved cavity. HpBPL shares extensive tertiary-structural similarity with Mycobacterium tuberculosis biotin protein ligase (MtBPL), despite having less than 22% sequence identity. The active site of HpBPL is very similar to that of MtBPL and has the necessary residues to bind inhibitors developed for MtBPL.

PubMed: 39704719
DOI: 10.1107/S2053230X24012056

Experimental method

X-RAY DIFFRACTION (2.25 Å)