Co-crystal structure of Helicobacter pylori biotin protein ligase with biotinyl-5-ATP.

Autor: Ayanlade JP; Dartmouth Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA., Davis DE; Dartmouth Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA., Subramanian S; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA., Dranow DM; Seattle Structural Genomics Center for Infectious Diseases, Seattle, Washington, USA., Lorimer DD; Seattle Structural Genomics Center for Infectious Diseases, Seattle, Washington, USA., Hammerson B; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA., Myler PJ; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA., Asojo OA; Dartmouth Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA.
Jazyk: angličtina
Zdroj: Acta crystallographica. Section F, Structural biology communications [Acta Crystallogr F Struct Biol Commun] 2025 Jan 01; Vol. 81 (Pt 1), pp. 11-18. Date of Electronic Publication: 2025 Jan 01.
DOI: 10.1107/S2053230X24012056
Abstrakt: 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.
(open access.)
Databáze: MEDLINE
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