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Metallomics : Integrated Biometal... Sep 2015Nickel is an essential micronutrient for a large number of living organisms, but it is also a toxic metal ion when it accumulates beyond the sustainable level as it may... (Review)
Review
Nickel is an essential micronutrient for a large number of living organisms, but it is also a toxic metal ion when it accumulates beyond the sustainable level as it may result if and when its cellular trafficking is not properly governed. Therefore, the homeostasis and metabolism of nickel is tightly regulated through metal-specific protein networks that respond to the available Ni(II) concentration. These are directed by specific nickel sensors, able to couple Ni(II) binding to a change in their DNA binding affinity and/or specificity, thus translating the cellular level of Ni(II) into a modification of the expression of the proteins devoted to modulating nickel uptake, efflux and cellular utilization. This review describes the Ni(II)-dependent transcriptional regulators discovered so far, focusing on their structural features, metal coordination modes and metal binding thermodynamics. Understanding these properties is essential to comprehend how these sensors correlate nickel availability to metal coordination and functional responses. A broad and comparative study, described here, reveals some general traits that characterize the binding stoichiometry and Ni(II) affinity of these metallo-sensors.
Topics: Amino Acid Sequence; Bacterial Proteins; Metalloproteins; Models, Molecular; Molecular Sequence Data; Nickel; Sequence Alignment; Thermodynamics; Transcription Factors
PubMed: 26099858
DOI: 10.1039/c5mt00072f -
The Journal of Biological Chemistry Mar 2018Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has... (Review)
Review
Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has toxic effects in cells, which is why eukaryotes and prokaryotes have evolved mechanisms for safe copper handling. A new family of bacterial proteins uses a Cys-rich four-helix bundle to safely store large quantities of Cu(I). The work leading to the discovery of these proteins, their properties and physiological functions, and how their presence potentially impacts the current views of bacterial copper handling and use are discussed in this review.
Topics: Bacteria; Bacterial Proteins; Copper; Metalloproteins
PubMed: 29414794
DOI: 10.1074/jbc.TM117.000180 -
Advances in Biochemical... 2023Metalloproteins, proteins containing metal atoms or clusters within their structures, are critical for various biological functions across all domains of life. More than...
Metalloproteins, proteins containing metal atoms or clusters within their structures, are critical for various biological functions across all domains of life. More than hundreds of different types have been discovered, which conduct various roles such as transportation of O, catalyzing chemical reactions, sensing environmental changes, and relaying electrons. Metalloprotein molecules incorporate a variety of metal atoms, coordinated to specific amino acid residues that affect their conformation and functionality. The process of metal incorporation typically occurs during or post-protein folding, often requiring chaperones for metal ion delivery and quality control. Progress in understanding metal incorporation and metalloprotein functionality has been enhanced by cell-free protein synthesis (CFPS) methods that offer direct control over the synthesis environment. This chapter reviews the diverse applications of CFPS methods in metalloprotein research, encompassing structure-function studies, protein engineering, and creation of artificial metalloproteins. Examples demonstrating the utility and advances brought about by CFPS in synthetic biology, electrochemistry, and drug discovery are highlighted. Despite remarkable progress, challenges remain in optimizing and advancing the CFPS methods, underscoring the need for future explorations in this transformative approach to metalloprotein study and engineering.
Topics: Metalloproteins; Metals; Amino Acids
PubMed: 37561181
DOI: 10.1007/10_2023_233 -
Journal of Inorganic Biochemistry Dec 2021Post-translational modifications (PTMs) are invaluable regulatory tools for the control of catalytic functionality, protein-protein interactions, and signaling pathways.... (Review)
Review
Post-translational modifications (PTMs) are invaluable regulatory tools for the control of catalytic functionality, protein-protein interactions, and signaling pathways. Historically, the study of phosphorylation as a PTM has been focused on serine, threonine, and tyrosine residues. In contrast, the significance of mammalian histidine phosphorylation remains largely unexplored. This gap in knowledge regarding the molecular basis for histidine phosphorylation as a regulatory agent exists in part because of the relative instability of phosphorylated histidine as compared with phosphorylated serine, threonine and tyrosine. However, the unique metal binding abilities of histidine make it one of the most common metal coordinating ligands in nature, and it is interesting to consider how phosphorylation would change the metal coordinating ability of histidine, and consequently, the properties of the phosphorylated metalloprotein. In this review, we examine eleven metalloproteins that have been shown to undergo reversible histidine phosphorylation at or near their metal binding sites. These proteins are described with respect to their biological activity and structure, with a particular emphasis on how phosphohistidine may tune the primary coordination sphere and protein conformation. Furthermore, several common methods, challenges, and limitations of studying sensitive, high affinity metalloproteins are discussed.
Topics: Amino Acid Sequence; Animals; Binding Sites; Histidine; Humans; Metalloproteins; Phosphorylation; Protein Processing, Post-Translational; Zinc Fingers
PubMed: 34555600
DOI: 10.1016/j.jinorgbio.2021.111606 -
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 -
Metallomics : Integrated Biometal... Jan 2018Nucleic acid enzymes (NAEs) are catalytically active RNA and DNA molecules. NAEs with RNA-cleaving activity are most extensively studied for applications in analytical... (Review)
Review
Nucleic acid enzymes (NAEs) are catalytically active RNA and DNA molecules. NAEs with RNA-cleaving activity are most extensively studied for applications in analytical chemistry, gene therapy and nanotechnology. Most NAEs require metal ions for activity. From a biochemical standpoint, these NAEs are reminiscent of metalloprotein enzymes with metal binding sites. While most NAEs require a single metal for the reaction, more and more recent examples have emerged that use two or even three metals for the reaction. The metal binding profile is sharper for these NAEs if they use the same metal ion due to cooperativity. Detailed studies have indicated examples of lanthanide and Ca binding DNAzymes, where the metals interact with the non-bridging oxygen atoms in the scissile phosphate, and these DNAzymes often have a very strong thio effect that cannot be rescued by adding thiophilic metals. Another type uses multiple different metals, where one metal interacts with the scissile phosphate and the other binds to the catalytic loop for allosteric interactions. Such allosteric NAEs can also be obtained via rational design or intentional selection based on existing NAEs. These multi-metal NAEs might be useful as logic gates with metal ions as inputs. In this article, we review different types of NAEs based on their use of metal ions. The NAEs reviewed include ribozymes, DNAzymes and rationally designed aptazymes. Finally, their emerging applications are discussed, and some future research opportunities are proposed.
Topics: Animals; DNA, Catalytic; Humans; Metalloproteins; Metals
PubMed: 29094140
DOI: 10.1039/c7mt00268h -
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 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 -
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