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Methods in Molecular Biology (Clifton,... 2019An overview of modern methods used in the preparation and characterization of molybdenum-containing enzymes is presented, with an emphasis on those methods that have...
An overview of modern methods used in the preparation and characterization of molybdenum-containing enzymes is presented, with an emphasis on those methods that have been developed over the past decade to address specific difficulties frequently encountered in studies of these enzymes.
Topics: Anaerobiosis; Metalloproteins; Molybdenum; Oxygen
PubMed: 30317474
DOI: 10.1007/978-1-4939-8864-8_4 -
Science Advances Sep 2022Inflammatory bowel disease (IBD) affects millions of people each year. The overproduction of reactive oxygen species (ROS) plays a critical role in the progress of IBD...
Inflammatory bowel disease (IBD) affects millions of people each year. The overproduction of reactive oxygen species (ROS) plays a critical role in the progress of IBD and will be a potential therapeutic target. Here, we synthesize a kind of oral zero-valent-molybdenum nanodots (ZVMNs) for the treatment of IBD by scavenging ROS. These ultrasmall ZVMNs can successfully pass through the gastric acid and then be absorbed by the intestine. It has been verified that ZVMNs can down-regulate the quantity of ROS and reduce colitis in a mouse IBD model without distinct side effects. In addition, RNA sequencing reveals a further mechanism that the ZVMNs can protect colon tissues from oxidative stress by inhibiting the nuclear factor κB signaling pathway and reducing the production of excessive pro-inflammatory factors. Together, the ZVMNs will offer a promising alternative treatment option for patients suffering from IBD.
Topics: Animals; Colitis; Disease Models, Animal; Inflammatory Bowel Diseases; Metal Nanoparticles; Mice; Molybdenum; NF-kappa B; Reactive Oxygen Species
PubMed: 36112678
DOI: 10.1126/sciadv.abp9882 -
Advances in Nutrition (Bethesda, Md.) May 2018Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for...
Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for lead, molybdenum was named after the Greek work molybdos, meaning lead-like. In the 1930s, it was recognized that ingestion of forage with high amounts of molybdenum by cattle caused a debilitating condition. In the 1950s, the essentiality of molybdenum was established with the discovery of the first molybdenum-containing enzymes. In humans, only 4 enzymes requiring molybdenum have been identified to date: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime-reducing component (mARC). Sulfite oxidase, an enzyme found in mitochondria, catalyzes oxidation of sulfite to sulfate, the final step in oxidation of sulfur amino acids (cysteine and methionine). Xanthine oxidase converts hypoxanthine to xanthine, and further converts xanthine to uric acid, preventing hypoxanthine, formed from spontaneous deamination of adenine, from leading to DNA mutations if paired with cytosine in place of thymine. Aldehyde oxidase is abundant in the liver and is an important enzyme in phase 1 drug metabolism. Finally, mARC, discovered less than a decade ago, works in concert with cytochrome b5 type B and NAD(H) cytochrome b5 reductase to reduce a variety of N-hydroxylated substrates, although the physiologic significance is still unclear. In the case of each of the molybdenum enzymes, activity is catalyzed via a tricyclic cofactor composed of a pterin, a dithiolene, and a pyran ring, called molybdenum cofactor (MoCo) (1).
Topics: Animals; Coenzymes; Cytochromes b5; Diet; Humans; Liver; Metalloproteins; Mitochondria; Molybdenum; Molybdenum Cofactors; Oxidoreductases; Pteridines; Trace Elements
PubMed: 29767695
DOI: 10.1093/advances/nmx001 -
Molecules (Basel, Switzerland) Jun 2023The mitochondrial amidoxime-reducing component (mARC) is the most recently discovered molybdoenzyme in humans after sulfite oxidase, xanthine oxidase and aldehyde... (Review)
Review
The mitochondrial amidoxime-reducing component (mARC) is the most recently discovered molybdoenzyme in humans after sulfite oxidase, xanthine oxidase and aldehyde oxidase. Here, the timeline of mARC's discovery is briefly described. The story begins with investigations into -oxidation of pharmaceutical drugs and model compounds. Many compounds are -oxidized extensively in vitro, but it turned out that a previously unknown enzyme catalyzes the reduction of the -oxygenated products in vivo. After many years, the molybdoenzyme mARC could finally be isolated and identified in 2006. mARC is an important drug-metabolizing enzyme and -reduction by mARC has been exploited very successfully for prodrug strategies, that allow oral administration of otherwise poorly bioavailable therapeutic drugs. Recently, it was demonstrated that mARC is a key factor in lipid metabolism and likely involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The exact link between mARC and lipid metabolism is not yet fully understood. Regardless, many now consider mARC a potential drug target for the prevention or treatment of liver diseases. This article focusses on discoveries related to mammalian mARC enzymes. mARC homologues have been studied in algae, plants and bacteria. These will not be discussed extensively here.
Topics: Animals; Humans; Oxidoreductases; Oxidation-Reduction; Sulfite Oxidase; Oximes; Mammals; Molybdenum
PubMed: 37375270
DOI: 10.3390/molecules28124713 -
Biosensors Jan 2022The use of nanoprobes in sensors is a popular way to amplify their analytical performance. Coupled with two-dimensional nanomaterials, nanoprobes have been widely used... (Review)
Review
The use of nanoprobes in sensors is a popular way to amplify their analytical performance. Coupled with two-dimensional nanomaterials, nanoprobes have been widely used to construct fluorescence, electrochemical, electrochemiluminescence (ECL), colorimetric, surface enhanced Raman scattering (SERS) and surface plasmon resonance (SPR) sensors for target molecules' detection due to their extraordinary signal amplification effect. The MoS nanosheet is an emerging layered nanomaterial with excellent chemical and physical properties, which has been considered as an ideal supporting substrate to design nanoprobes for the construction of sensors. Herein, the development and application of molybdenum disulfide (MoS)-based nanoprobes is reviewed. First, the preparation principle of MoS-based nanoprobes was introduced. Second, the sensing application of MoS-based nanoprobes was summarized. Finally, the prospect and challenge of MoS-based nanoprobes in future were discussed.
Topics: Disulfides; Molybdenum; Nanostructures; Surface Plasmon Resonance
PubMed: 35200348
DOI: 10.3390/bios12020087 -
Molecules (Basel, Switzerland) Aug 2022For most organisms molybdenum is essential for life as it is found in the active site of various vitally important molybdenum dependent enzymes (Mo-enzymes). Here,... (Review)
Review
For most organisms molybdenum is essential for life as it is found in the active site of various vitally important molybdenum dependent enzymes (Mo-enzymes). Here, molybdenum is bound to a pterin derivative called molybdopterin (MPT), thus forming the molybdenum cofactor (Moco). Synthesis of Moco involves the consecutive action of numerous enzymatic reaction steps, whereby molybdenum insertases (Mo-insertases) catalyze the final maturation step, i.e., the metal insertion reaction yielding Moco. This final maturation step is subdivided into two partial reactions, each catalyzed by a distinctive Mo-insertase domain. Initially, MPT is adenylylated by the Mo-insertase G-domain, yielding MPT-AMP which is used as substrate by the E-domain. This domain catalyzes the insertion of molybdate into the MPT dithiolene moiety, leading to the formation of Moco-AMP. Finally, the Moco-AMP phosphoanhydride bond is cleaved by the E-domain to liberate Moco from its synthesizing enzyme. Thus formed, Moco is physiologically active and may be incorporated into the different Mo-enzymes or bind to carrier proteins instead.
Topics: Adenosine Monophosphate; Catalytic Domain; Coenzymes; Metalloproteins; Molybdenum; Molybdenum Cofactors; Pterins
PubMed: 36080140
DOI: 10.3390/molecules27175372 -
Molecules (Basel, Switzerland) Jun 2022Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build active site analogues. These... (Review)
Review
Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build active site analogues. These studies not only led to an ever more detailed mechanistic understanding of the biological template, but also paved the way to atypical selectivity and activity, such as catalytic hydrogen evolution. This review is aimed at representing the last decade's progress in the research of and with molybdenum and tungsten functional model compounds. The portrayed systems, organized according to their ability to facilitate typical and artificial enzyme reactions, comprise complexes with dithiolene ligands, resembling molybdopterin, as well as entirely non-natural nitrogen, oxygen, and/or sulfur bearing chelating donor ligands. All model compounds receive individual attention, highlighting the specific novelty that each provides for our understanding of the enzymatic mechanisms, such as oxygen atom transfer and proton-coupled electron transfer, or that each presents for exploiting new and useful catalytic capability. Overall, a shift in the application of these model compounds towards uncommon reactions is noted, the latter are comprehensively discussed.
Topics: Iron-Sulfur Proteins; Ligands; Molybdenum; Organometallic Compounds; Oxidoreductases; Oxygen; Tungsten
PubMed: 35744820
DOI: 10.3390/molecules27123695 -
Molecules (Basel, Switzerland) Oct 2022The molybdenum cofactor (Moco) is the active site prosthetic group found in numerous vitally important enzymes (Mo-enzymes), which predominantly catalyze 2 electron... (Review)
Review
The molybdenum cofactor (Moco) is the active site prosthetic group found in numerous vitally important enzymes (Mo-enzymes), which predominantly catalyze 2 electron transfer reactions. Moco is synthesized by an evolutionary old and highly conserved multi-step pathway, whereby the metal insertion reaction is the ultimate reaction step here. Moco and its intermediates are highly sensitive towards oxidative damage and considering this, they are believed to be permanently protein bound during synthesis and also after Moco maturation. In plants, a cellular Moco transfer and storage system was identified, which comprises proteins that are capable of Moco binding and release but do not possess a Moco-dependent enzymatic activity. The first protein described that exhibited these properties was the Moco carrier protein (MCP) from the green alga . However, MCPs and similar proteins have meanwhile been described in various plant species. This review will summarize the current knowledge of the cellular Moco distribution system.
Topics: Carrier Proteins; Catalytic Domain; Chlamydomonas reinhardtii; Coenzymes; Metalloproteins; Molybdenum; Molybdenum Cofactors; Plants
PubMed: 36235107
DOI: 10.3390/molecules27196571 -
Molecules (Basel, Switzerland) May 2022Pterins are bicyclic heterocycles that are found widely across Nature and are involved in a variety of biological functions. Notably, pterins are found at the core of... (Review)
Review
Pterins are bicyclic heterocycles that are found widely across Nature and are involved in a variety of biological functions. Notably, pterins are found at the core of molybdenum cofactor (Moco) containing enzymes in the molybdopterin (MPT) ligand that coordinates molybdenum and facilitates cofactor activity. Pterins are diverse and can be widely functionalized to tune their properties. Herein, the general methods of synthesis, redox and spectroscopic properties of pterin are discussed to provide more insight into pterin chemistry and their importance to biological systems.
Topics: Molybdenum; Molybdenum Cofactors; Oxidation-Reduction; Pterins; Spectrum Analysis
PubMed: 35630801
DOI: 10.3390/molecules27103324 -
The Journal of Biological Chemistry May 2013The transition element molybdenum needs to be complexed by a special cofactor to gain catalytic activity. Molybdenum is bound to a unique pterin, thus forming the... (Review)
Review
The transition element molybdenum needs to be complexed by a special cofactor to gain catalytic activity. Molybdenum is bound to a unique pterin, thus forming the molybdenum cofactor (Moco), which, in different variants, is the active compound at the catalytic site of all molybdenum-containing enzymes in nature, except bacterial molybdenum nitrogenase. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also require iron, ATP, and copper. After its synthesis, Moco is distributed, involving Moco-binding proteins. A deficiency in the biosynthesis of Moco has lethal consequences for the respective organisms.
Topics: Animals; Biosynthetic Pathways; Coenzymes; Humans; Metalloexopeptidases; Metalloproteins; Molybdenum; Molybdenum Cofactors; Organophosphorus Compounds; Pteridines; Pterins
PubMed: 23539623
DOI: 10.1074/jbc.R113.455311