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Thiamine and Thiamine Pyrophosphate as Non-Competitive Inhibitors of Acetylcholinesterase-Experimental and Theoretical Investigations.
Molecules
January 2025
Chair and Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.
Vitamin B (thiamine) plays an important role in human metabolism. It is essential for the proper growth and development of the body and has a positive effect on the functioning of the digestive, cardiovascular, and nervous systems. Additionally, it stimulates the brain and improves the psycho-emotional state.
View Article and Find Full Text PDFScaffold-enabled high-resolution cryo-EM structure determination of RNA.
Nat Commun
January 2025
Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA.
Cryo-EM structure determination of protein-free RNAs has remained difficult with most attempts yielding low to moderate resolution and lacking nucleotide-level detail. These difficulties are compounded for small RNAs as cryo-EM is inherently more difficult for lower molecular weight macromolecules. Here we present a strategy for fusing small RNAs to a group II intron that yields high resolution structures of the appended RNA.
View Article and Find Full Text PDFApo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.
Biochem Biophys Res Commun
February 2025
Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands. Electronic address:
The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme.
View Article and Find Full Text PDFMetal-organic framework-based nanoplatforms for synergistic anti-atherosclerosis therapy by regulating the PI3K/AKT/MSR1 pathway in macrophages.
Nanoscale
December 2024
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Atherosclerosis is the main pathogenic factor of various cardiovascular diseases. During the pathogenesis of atherosclerosis, macrophages play a major role, mainly by secreting pro-inflammatory cytokines and taking in lipids to form foam cells. Thiamine pyrophosphate (TPP) is an antagonist of the P2Y6 receptor, which is overexpressed on macrophages during atherosclerosis and facilitates the lipid phagocytosis of macrophages.
View Article and Find Full Text PDFGold Nanoparticles Decorated CoAl LDH Monolayer: A Peroxidase-Like Nanozyme for Sensitive Colorimetric Detection of Acetylcholinesterase and Inhibitors.
Inorg Chem
December 2024
Department of Laboratory Medicine/Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Monitoring acetylcholinesterase (AChE) activity and its inhibitor is crucial yet challenging for the early diagnosis and treatment of neurological diseases. In this study, we present Au nanoparticle decorated CoAl layered double hydroxide monolayer (Au@CoAl-LDH-m) as a peroxidase-like (POD) nanozyme for the sensitive colorimetric detection of AChE and its inhibitor, thiamine pyrophosphate (TPP). Remarkably, the Au@CoAl-LDH-m nanozyme can catalyze the oxidation of chromogenic substrates through its POD-like activity, which is effectively inhibited by thiocholine (TCh, a catalytic product of AChE), thereby enabling detection of AChE and TPP through a visible colorimetric readout.
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