Phosphatidylinositol 4-phosphate (PI4P) is the most abundant monophosphoinositide in eukaryotic cells. Humans have four phosphatidylinositol 4-kinases (PI4Ks) that synthesize PI4P, among which are PI4K IIβ and PI4K IIα. In this study, two crystal structures are presented: the structure of human PI4K IIβ and the structure of PI4K IIα containing a nucleoside analogue. The former, a complex with ATP, is the first high-resolution (1.9 Å) structure of a PI4K. These structures reveal new details such as high conformational heterogeneity of the lateral hydrophobic pocket of the C-lobe and together provide a structural basis for isoform-specific inhibitor design.

Download full-text PDF

Source
http://dx.doi.org/10.1107/S1399004715009505DOI Listing

Publication Analysis

Top Keywords

crystal structure
8
structure phosphatidylinositol
8
phosphatidylinositol 4-kinase
8
iiα nucleoside
8
nucleoside analogue
8
provide structural
8
structural basis
8
basis isoform-specific
8
isoform-specific inhibitor
8
inhibitor design
8

Similar Publications

Structural insights into the role of the prosegment binding loop in a papain-superfamily cysteine protease from Treponema denticola.

Acta Crystallogr F Struct Biol Commun

February 2025

Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

Periodontal diseases afflict 20-50% of the global population and carry serious health and economic burdens. Chronic periodontitis is characterized by inflammation of the periodontal pocket caused by dysbiosis. This dysbiosis is coupled with an increase in the population of Treponema denticola, a spirochete bacterium with high mobility and invasivity mediated by a number of virulence factors.

View Article and Find Full Text PDF

Polyphosphate kinases (PPK) play crucial roles in various biological processes, including energy storage and stress responses, through their interaction with inorganic polyphosphate (polyP) and the intracellular nucleotide pool. Members of the PPK family 2 (PPK2s) catalyse polyP‑consuming phosphorylation of nucleotides. In this study, we characterised two PPK2 enzymes from Bacillus cereus (BcPPK2) and Lysinibacillus fusiformis (LfPPK2) to investigate their substrate specificity and potential for selective nucleotide synthesis.

View Article and Find Full Text PDF

β-Addition products are common in conjugate addition reactions consisting of α,β-unsaturated carbonyl compounds. Here, we are reporting an uncommon α-addition product as a major product in the thioacetic acid conjugate addition reaction on a peptide consisting of ()-α,β-unsaturated γ-amino acids. In addition, we observed highly diastereoselective β-addition products from the thiophenol and thioethanol conjugate addition reaction on peptides.

View Article and Find Full Text PDF

Eicosapentaenoic acid as an antibiofilm agent disrupts mature biofilms of .

Biofilm

June 2025

Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

The biofilm formation of , a major human fungal pathogen, represents a crucial virulence factor during candidiasis. Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, has emerged as a potential antibiofilm agent against . .

View Article and Find Full Text PDF

In this study, the effect of feedstock concentration on the synthesis of WO nanostructures in a one-step hydrothermal process was investigated. According to our experiments, when titrating aqueous NaWO·2HO with HCl solutions of different concentrations to a constant pH of 1.5, after identical hydrothermal treatments at 180 °C, the morphology, crystal size and phase composition as well as the optical properties of the products could be tuned.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!