AI Article Synopsis
- Helicobacter pylori is a type 1 carcinogen linked to gastric ulcers and cancer, and research by the Seattle Structural Genomics Center for Infectious Disease focuses on potential treatments targeting this bacterium.
- The study reports on the purification and crystallization of H. pylori biotin protein ligase (HpBPL), an enzyme that plays a crucial role in important metabolic processes and helps H. pylori thrive in the acidic environment of the stomach.
- Despite having low sequence identity with similar proteins, HpBPL shares significant structural similarities with Mycobacterium tuberculosis biotin protein ligase, indicating potential for developing inhibitors that could be effective against HpBPL.
Article 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.
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| http://dx.doi.org/10.1107/S2053230X24012056 | DOI Listing |
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Article Synopsis
- Helicobacter pylori is a type 1 carcinogen linked to gastric ulcers and cancer, and research by the Seattle Structural Genomics Center for Infectious Disease focuses on potential treatments targeting this bacterium.
- The study reports on the purification and crystallization of H. pylori biotin protein ligase (HpBPL), an enzyme that plays a crucial role in important metabolic processes and helps H. pylori thrive in the acidic environment of the stomach.
- Despite having low sequence identity with similar proteins, HpBPL shares significant structural similarities with Mycobacterium tuberculosis biotin protein ligase, indicating potential for developing inhibitors that could be effective against HpBPL.
The proximity interactome of PML isoforms I and II under fatty acid stress.
FEBS Lett
December 2024
Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Canada.
Promyelocytic leukemia (PML) protein forms the scaffold for PML nuclear bodies (PML NB) that reorganize into Lipid-Associated PML Structures (LAPS) under fatty acid stress. We determined how the fatty acid oleate alters the interactome of PMLI or PMLII by expressing fusions with the ascorbate peroxidase APEX2 in U2OS cells. The resultant interactome included ESCRT and COPII transport protein nodes.
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