Track topics on Twitter Track topics that are important to you
Human aldehyde oxidase (hAOX1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX1 metabolizes different classes of xenobiotics and is one of the main drug-metabolizing enzymes in the liver, along with cytochrome P450. hAOX1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug-metabolizing enzymes caused by single nucleotide polymorphisms (SNPs) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)-free form of hAOX1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild-type hAOX1 and hAOX1 with various SNPs (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and ThermoFAD, revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 °C. These results correlated with biochemical and structural data and enhance our understanding of hAOX1 and the effect of SNPs in the gene encoding this enzyme in the human population.
Aldehyde oxidase (EC220.127.116.11); xanthine dehydrogenase (EC18.104.22.168); xanthine oxidase (EC22.214.171.124).
Structural data are available in the Protein Data Bank under the accession number 6Q6Q.
This article was published in the following journal.
Name: FEBS open bio
In cereal crops, ABA deficiency during seed maturation phase causes pre-harvest sprouting (PHS), and molybdenum cofactor (MoCo) is required for ABA biosynthesis. Here, two rice PHS mutants F254 and F5...
The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production fr...
This paper reports on a colorimetric assay for HO and glucose. It is based on the use of human serum albumin-templated MnO nanosheets that possess oxidase-like activity. They are capable of oxidizing...
Hydralazine has been reported as a selective mechanism-based inactivator of aldehyde oxidase (AO) and it is widely used in the pharmaceutical industry for reaction phenotyping to estimate fraction met...
Human aldehyde oxidase 1 (AOX1) catalyzes the oxidation of various drugs and endogenous compounds. Recently, we found that AOX1 catalyzed the reduction of drugs such as nitrazepam and dantrolene. In t...
DAOsin is a food supplement for special medical purpose for the treatment of food intolerance provoked by histamine intake. In this uncontrolled, interventional pilot study the effect of a...
This is a randomized, parallel, single center, double masked, vehicle controlled study. The purpose of this study is to determine the activity and safety of NS2 in patients with grass, tre...
Adjuvant N-methyl-D-aspartic acid (NMDA)-enhancing agents, such as GlyT-1 inhibitors and NMDA-glycine site agonists have been demonstrated to be beneficial for chronic schizophrenia patien...
Obstructive Sleep Apnea (OSA) is associated with increased oxidative stress. The major sources of Reactive Oxygen Species (ROS) in the vasculature are the NADPH oxidases. Several polymorph...
Our recent data in mice have demonstrated a key role of xanthine oxidase in hyperglycemia-induced by Reactive oxygen species production, and a preventive role of allopurinol (inhibitor of ...
An aldehyde oxidoreductase expressed predominantly in the LIVER; LUNGS; and KIDNEY. It catalyzes the oxidation of a variety of organic aldehydes and N-heterocyclic compounds to CARBOXYLIC ACIDS, and also oxidizes quinoline and pyridine derivatives. The enzyme utilizes molybdenum cofactor and FAD as cofactors.
A metallic element with the atomic symbol Mo, atomic number 42, and atomic weight 95.94. It is an essential trace element, being a component of the enzymes xanthine oxidase, aldehyde oxidase, and nitrate reductase. (From Dorland, 27th ed)
A fluorescent calcium chelating agent which is used to study intracellular calcium in many tissues. The fluorescent and chelating properties of Fura-2 aid in the quantitation of endothelial cell injury, in monitoring ATP-dependent calcium uptake by membrane vesicles, and in the determination of the relationship between cytoplasmic free calcium and oxidase activation in rat neutrophils.
Gastric analysis for determination of free acid or total acid.
An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 126.96.36.199.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...