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Current Opinion in Chemical Biology Oct 2023Microbes utilize numerous metal cofactor-containing proteins to recognize and respond to constantly fluctuating redox stresses in their environment. Gaining an... (Review)
Review
Microbes utilize numerous metal cofactor-containing proteins to recognize and respond to constantly fluctuating redox stresses in their environment. Gaining an understanding of how these metalloproteins sense redox events, and how they communicate such information downstream to DNA to modulate microbial metabolism, is a topic of great interest to both chemists and biologists. In this article, we review recently characterized examples of metalloprotein sensors, focusing on the coordination and oxidation state of the metals involved, how these metals are able to recognize redox stimuli, and how the signal is transmitted beyond the metal center. We discuss specific examples of iron, nickel, and manganese-based microbial sensors, and identify gaps in knowledge in the field of metalloprotein-based signal transduction pathways.
Topics: Metalloproteins; Metals; Iron; Oxidation-Reduction; Signal Transduction
PubMed: 37311385
DOI: 10.1016/j.cbpa.2023.102331 -
MBio Dec 2021Building iron-sulfur (Fe-S) clusters and assembling Fe-S proteins are essential actions for life on Earth. The three processes that sustain life, photosynthesis,... (Review)
Review
Building iron-sulfur (Fe-S) clusters and assembling Fe-S proteins are essential actions for life on Earth. The three processes that sustain life, photosynthesis, nitrogen fixation, and respiration, require Fe-S proteins. Genes coding for Fe-S proteins can be found in nearly every sequenced genome. Fe-S proteins have a wide variety of functions, and therefore, defective assembly of Fe-S proteins results in cell death or global metabolic defects. Compared to alternative essential cellular processes, there is less known about Fe-S cluster synthesis and Fe-S protein maturation. Moreover, new factors involved in Fe-S protein assembly continue to be discovered. These facts highlight the growing need to develop a deeper biological understanding of Fe-S cluster synthesis, holo-protein maturation, and Fe-S cluster repair. Here, we outline bacterial strategies used to assemble Fe-S proteins and the genetic regulation of these processes. We focus on recent and relevant findings and discuss future directions, including the proposal of using Fe-S protein assembly as an antipathogen target.
Topics: Bacteria; Bacterial Proteins; Iron; Iron-Sulfur Proteins; Sulfur
PubMed: 34781750
DOI: 10.1128/mBio.02425-21 -
Journal of Enzyme Inhibition and... Dec 2023Urease is a kind of nickel-dependent metalloenzyme, which exists in the biological world widely, and can catalyse the hydrolysis of urea into ammonia and carbon dioxide... (Review)
Review
Urease is a kind of nickel-dependent metalloenzyme, which exists in the biological world widely, and can catalyse the hydrolysis of urea into ammonia and carbon dioxide to provide a nitrogen source for organisms. Urease has important uses in agriculture and medicine because it can catalyse the production of ammonia. Therefore, in this review, metal-based inhibitors of urease will be summarised according to different transition metal ions. Including the urease inhibition, structure-activity relationship, and molecular docking. Importantly, among these reviewed effective urease inhibitors, most of copper metal complexes exhibited stronger urease inhibition with IC values ranging from 0.46 μM to 41.1 μM. Significantly, the collected comprehensive information looks forward to providing rational guidance and effective strategies for the development of novel, potent, and safe metal-based urease inhibitors, which are better for practical applications in the future.
Topics: Urease; Ammonia; Molecular Docking Simulation; Metals; Metalloproteins
PubMed: 36446640
DOI: 10.1080/14756366.2022.2150182 -
Cardiology in ReviewZinc is an essential trace element due to its role as a key part of human enzymatic activity. As a cofactor in metalloenzymes and metalloproteins, zinc participates in... (Review)
Review
Zinc is an essential trace element due to its role as a key part of human enzymatic activity. As a cofactor in metalloenzymes and metalloproteins, zinc participates in diverse biological functions, including gene transcription, translation, and replication, phagocytosis, and immunoglobulin and cytokine production. In this review, we will focus on the role of zinc in the cardiovascular system, including heart failure, vascular calcification, and myocardial infarction. We will further highlight the role of zinc in cardiovascular pathology in individuals with chronic kidney disease, and type II diabetes mellitus, groups uniquely at risk for cardiovascular morbidity and mortality.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Metalloproteins; Renal Insufficiency, Chronic; Zinc
PubMed: 35119422
DOI: 10.1097/CRD.0000000000000382 -
Annual Review of Biochemistry Jun 2022Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many... (Review)
Review
Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many diseases. Metals are also frequently incorporated into diagnosis and therapeutics. Understanding of metal homeostasis under (patho)physiological conditions and the molecular mechanisms of action of metallodrugs in biological systems has positive impacts on human health. As an emerging interdisciplinary area of research, metalloproteomics involves investigating metal-protein interactions in biological systems at a proteome-wide scale, has received growing attention, and has been implemented into metal-related research. In this review, we summarize the recent advances in metalloproteomics methodologies and applications. We also highlight emerging single-cell metalloproteomics, including time-resolved inductively coupled plasma mass spectrometry, mass cytometry, and secondary ion mass spectrometry. Finally, we discuss future perspectives in metalloproteomics, aiming to attract more original research to develop more advanced methodologies, which could be utilized rapidly by biochemists or biologists to expand our knowledge of how metal functions in biology and medicine.
Topics: Biomedical Research; Humans; Metalloproteins; Metals; Proteome; Proteomics
PubMed: 35303792
DOI: 10.1146/annurev-biochem-040320-104628 -
Molecules (Basel, Switzerland) Jan 2021In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and... (Review)
Review
In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and rapid development in industrial processes over a similar timeline. Therefore, there is a pressing need to understand the structure and function of proteins in novel environments with ILs. Understanding the short-term and long-term stability of protein molecules in IL formulations will be key to using ILs for protein technologies. Similarly, ILs have been investigated as part of therapeutic delivery systems and implicated in numerous studies in which ILs impact the activity and/or stability of protein molecules. Notably, many of the proteins used in industrial applications are involved in redox chemistry, and thus often contain metal ions or metal-associated cofactors. In this review article, we focus on the current understanding of protein structure-function relationship in the presence of ILs, specifically focusing on the effect of ILs on metal containing proteins.
Topics: Ionic Liquids; Metalloproteins; Structure-Activity Relationship
PubMed: 33478102
DOI: 10.3390/molecules26020514 -
Chemical Reviews May 2022Paramagnetic centers in biomolecules, such as specific metal ions that are bound to a protein, affect the nuclei in their surrounding in various ways. One of these... (Review)
Review
Paramagnetic centers in biomolecules, such as specific metal ions that are bound to a protein, affect the nuclei in their surrounding in various ways. One of these effects is the pseudocontact shift (PCS), which leads to strong chemical shift perturbations of nuclear spins, with a remarkably long range of 50 Å and beyond. The PCS in solution NMR is an effect originating from the anisotropic part of the dipole-dipole interaction between the magnetic momentum of unpaired electrons and nuclear spins. The PCS contains spatial information that can be exploited in multiple ways to characterize structure, function, and dynamics of biomacromolecules. It can be used to refine structures, magnify effects of dynamics, help resonance assignments, allows for an intermolecular positioning system, and gives structural information in sensitivity-limited situations where all other methods fail. Here, we review applications of the PCS in biomolecular solution NMR spectroscopy, starting from early works on natural metalloproteins, following the development of non-natural tags to chelate and attach lanthanoid ions to any biomolecular target to advanced applications on large biomolecular complexes and inside living cells. We thus hope to not only highlight past applications but also shed light on the tremendous potential the PCS has in structural biology.
Topics: Ions; Lanthanoid Series Elements; Magnetic Resonance Spectroscopy; Metalloproteins; Nuclear Magnetic Resonance, Biomolecular; Protein Conformation
PubMed: 35005884
DOI: 10.1021/acs.chemrev.1c00796 -
Chemical Society Reviews Jul 2020Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and... (Review)
Review
Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and adverse health threats of some fluorochemicals, the development of new methods for their decomposition is significant to public health. However, the carbon-fluorine (C-F) bond is among the most chemically robust bonds; consequently, the degradation of fluorinated hydrocarbons is exceptionally difficult. Here, metalloenzymes that catalyze the cleavage of this chemically challenging bond are reviewed. These enzymes include histidine-ligated heme-dependent dehaloperoxidase and tyrosine hydroxylase, thiolate-ligated heme-dependent cytochrome P450, and four nonheme oxygenases, namely, tetrahydrobiopterin-dependent aromatic amino acid hydroxylase, 2-oxoglutarate-dependent hydroxylase, Rieske dioxygenase, and thiol dioxygenase. While much of the literature regarding the aforementioned enzymes highlights their ability to catalyze C-H bond activation and functionalization, in many cases, the C-F bond cleavage has been shown to occur on fluorinated substrates. A copper-dependent laccase-mediated system representing an unnatural radical defluorination approach is also described. Detailed discussions on the structure-function relationships and catalytic mechanisms provide insights into biocatalytic defluorination, which may inspire drug design considerations and environmental remediation of halogenated contaminants.
Topics: Carbon; Fluorine; Metalloproteins
PubMed: 32510080
DOI: 10.1039/c9cs00740g -
Journal of Inorganic Biochemistry Oct 2022Resonance Raman spectroscopy (rR) is a powerful spectroscopic probe that is widely used for studying the geometric and electronic structure of metalloproteins. In this... (Review)
Review
Resonance Raman spectroscopy (rR) is a powerful spectroscopic probe that is widely used for studying the geometric and electronic structure of metalloproteins. In this focused review, we detail how resonance Raman spectroscopy has contributed to a greater understanding of electronic structure, geometric structure, and the reaction mechanisms of pyranopterin molybdenum enzymes. The review focuses on the enzymes sulfite oxidase (SO), dimethyl sulfoxide reductase (DMSOR), xanthine oxidase (XO), and carbon monoxide dehydrogenase. Specifically, we highlight how Mo-O, Mo-S, Mo-S, and dithiolene CC vibrational modes, isotope and heavy atom perturbations, resonance enhancement, and associated Raman studies of small molecule analogs have provided detailed insight into the nature of these metalloenzyme active sites.
Topics: Coenzymes; Metalloproteins; Models, Molecular; Molybdenum; Pterins; Spectrum Analysis, Raman
PubMed: 35932756
DOI: 10.1016/j.jinorgbio.2022.111907 -
Current Opinion in Chemical Biology Feb 2022Artificial metalloenzymes (ArMs) utilize the best properties of homogenous transition metal catalysts and naturally occurring proteins. While synthetic metal complexes... (Review)
Review
Artificial metalloenzymes (ArMs) utilize the best properties of homogenous transition metal catalysts and naturally occurring proteins. While synthetic metal complexes offer high tunability and broad-scope reactivity with a variety of substrates, enzymes further endow these complexes with enhanced aqueous stability and stereoselectivity. For these reasons, dozens of ArMs have been designed to perform catalytic asymmetric hydrogenation reactions, and hydrogenase ArMs are, in fact, the oldest class of ArMs. Herein, we report recent advances in the design of hydrogenase ArMs, including (i) the modification of natural [Fe]-hydrogenase by insertion of artificial metallocofactors, (ii) design of a novel ArM system from the tractable and inexpensive protein β-lactoglobulin to afford a high-performing transfer hydrogenase, and (iii) the design of chimeric streptavidin scaffolds that drastically alter the secondary coordination sphere of previously reported streptavidin/biotin transfer hydrogenase ArMs.
Topics: Biotin; Catalysis; Hydrogenation; Metalloproteins; Streptavidin
PubMed: 34879303
DOI: 10.1016/j.cbpa.2021.102096