N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs …

A Golovanov, A Zhuravlev, A Cruz… - Journal of medicinal …, 2022 - ACS Publications
Here, we describe the first systematic study on the mechanism of substrate-selective
inhibition of mammalian ALOX15 orthologs. For this purpose, we prepared a series of N …

13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme–Substrate Complex of an …

A Sharma, C Whittington, M Jabed, SG Hill… - Biochemistry, 2023 - ACS Publications
Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to
capture and characterize LOX–substrate complexes by X-ray co-crystallography are …

Human lipoxygenase isoforms form complex patterns of double and triple oxygenated compounds from eicosapentaenoic acid

L Kutzner, K Goloshchapova, KM Rund… - … et Biophysica Acta (BBA …, 2020 - Elsevier
Lipoxygenases (ALOX) are lipid peroxidizing enzymes that catalyze the biosynthesis of pro-
and anti-inflammatory lipid mediators and have been implicated in (patho-) physiological …

The reaction specificity of mammalian ALOX15 orthologs is changed during late primate evolution and these alterations might offer evolutionary advantages for …

D Heydeck, F Reisch, M Schäfer… - Frontiers in cell and …, 2022 - frontiersin.org
Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of
mammals. The reaction specificity of these enzymes is decisive for their biological functions …

Identification of the Thermal Activation Network in Human 15-Lipoxygenase-2: Divergence from Plant Orthologs and Its Relationship to Hydrogen Tunneling Activation …

A Ohler, PE Taylor, JA Bledsoe, AT Iavarone… - ACS …, 2024 - ACS Publications
The oxidation of polyunsaturated fatty acids by lipoxygenases (LOXs) is initiated by a C–H
cleavage step in which the hydrogen atom is transferred quantum mechanically (ie, via …

Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice

E Marbach-Breitrück, N Rohwer, C Infante-Duarte… - Metabolites, 2021 - mdpi.com
Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-
inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an …

Functional Characterization of transgenic mice overexpressing human 15-Lipoxygenase-1 (ALOX15) under the control of the aP2 promoter

D Heydeck, C Ufer, KR Kakularam, M Rothe… - International journal of …, 2023 - mdpi.com
Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of
inflammatory, hyperproliferative, neurodegenerative, and metabolic diseases, but the …

Mutations of triad determinants changes the substrate alignment at the catalytic center of human ALOX5

I Ivanov, AB Golovanov, C Ferretti… - ACS chemical …, 2019 - ACS Publications
For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino
acids Phe353, Ile418, Met419, and Ile593 (“triad determinants”) is important, and …

Functional Characterization of Novel Bony Fish Lipoxygenase Isoforms and Their Possible Involvement in Inflammation

S Roigas, D Heydeck, H Kuhn - International Journal of Molecular …, 2022 - mdpi.com
Eicosanoids and related compounds are pleiotropic lipid mediators, which are
biosynthesized in mammals via three distinct metabolic pathways (cyclooxygenase pathway …

Structural and functional evaluation mammalian and plant lipoxygenases upon association with nanodics as membrane mimetics

S Ulusan, I Sheraj, S Stehling, I Ivanov, A Das… - Biophysical …, 2022 - Elsevier
Lipoxygenases (LOX) are a family lipid oxygenating enzymes that can generate bioactive
lipids of clinical relevance from polyunsaturated fatty acids. Most LOXs display a Ca 2+ …