Lipoxygenases (LOXs) are a key part of several signaling pathways that lead to inflammation and cancer. Yet, the mechanisms of substrate binding and allosteric regulation by the various LOX isoforms remain speculative. Here we report the 2.47-Å resolution crystal structure of the arachidonate 11R-LOX from Gersemia fruticosa, which sheds new light on the mechanism of LOX catalysis. Our crystallographic and mutational studies suggest that the aliphatic tail of the fatty acid is bound in a hydrophobic pocket with two potential entrances. We speculate that LOXs share a common T-shaped substrate channel architecture that gives rise to the varying positional specificities. A general allosteric mechanism is proposed for transmitting the activity-inducing effect of calcium binding from the membrane-targeting PLAT (polycystin-1/lipoxygenase/α-toxin) domain to the active site via a conserved π-cation bridge.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381197 | PMC |
| http://dx.doi.org/10.1074/jbc.M112.343285 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Activation of TMEM16E scramblase induces ligand independent growth factor receptor signaling and macropinocytosis for membrane repair.
Commun Biol
January 2025
Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
The calcium-dependent phospholipid scramblase TMEM16E mediates ion transport and lipid translocation across the plasma membrane. TMEM16E also contributes to protection of membrane structure by facilitating cellular repair signaling. Our research reveals that TMEM16E activation promotes macropinocytosis, essential for maintaining plasma membrane integrity.
View Article and Find Full Text PDFIdentification and functional analysis of a novel L-type lectin (NdLTL1) from Neocaridina denticulata sinensis.
Fish Shellfish Immunol
January 2025
School of Life Sciences/Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, 071002, China; Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China. Electronic address:
This study investigates an L-type lectin, NdLTL1, derived from Neocaridina denticulata sinensis, emphasizing its role in immune defense through carbohydrate binding and bacterial agglutination. Bioinformatics analysis identified 179 lectin sequences, leading to subsequent investigations into the structure and function of NdLTL1. The open reading frame (ORF) of NdLTL1 spans 966 bp and encodes a protein consisting of 321 amino acids (36.
View Article and Find Full Text PDFThe RNA-binding properties of Annexins.
J Mol Biol
January 2025
Elettra Sincrotrone Trieste, Italy; The Wohl Institute, King's College London, 5 Cutcombe Rd, SW59RT London, UK. Electronic address:
Annexins are a family of calcium-dependent phospholipid-binding proteins involved in crucial cellular processes such as cell division, calcium signaling, vesicle trafficking, membrane repair, and apoptosis. In addition to these properties, Annexins have also been shown to bind RNA, although this function is not universally recognized. In the attempt to clarify this important issue, we employed an integrated combination of experimental and computational approaches.
View Article and Find Full Text PDFInsights into Structure and Function of Growth Arrest Specific 2 (GAS2).
J Cancer
January 2025
Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Growth arrest specific 2 (GAS2) is a microfilament-associated protein, which is widely distributed in human tissues. It exerts a pivotal influence on various cellular processes, including cytoskeletal regulation, cell cycle progression, apoptosis, and senescence. GAS2 has a dual function in cancer cell growth: on the one hand, it enhances the sensitivity of cancer cells to chemoradiotherapy and prevents malignant transformation of normal cells; but on the other hand, it maintains the growth of cancer cells.
View Article and Find Full Text PDFEffects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential.
Adv Sci (Weinh)
December 2024
Department of Kidney Research Institute, Seoul National University Medical Research Center, Seoul, South Korea.
Podocyte injury and proteinuria in glomerular disease are critical indicators of acute kidney injury progression to chronic kidney disease. Renal mitochondrial dysfunction, mediated by intracellular calcium levels and oxidative stress, is a major contributor to podocyte complications. Despite various strategies targeting mitochondria to improve kidney function, effective treatments remain lacking.
View Article and Find Full Text PDFWant 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!