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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 -
Cell Jun 2022Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins in living organisms. During Zn limitation, specialized enzymes called metallochaperones...
Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins in living organisms. During Zn limitation, specialized enzymes called metallochaperones are predicted to allocate Zn to specific metalloproteins. This function has been putatively assigned to G3E GTPase COG0523 proteins, yet no Zn metallochaperone has been experimentally identified in any organism. Here, we functionally characterize a family of COG0523 proteins that is conserved across vertebrates. We identify Zn metalloprotease methionine aminopeptidase 1 (METAP1) as a COG0523 client, leading to the redesignation of this group of COG0523 proteins as the Zn-regulated GTPase metalloprotein activator (ZNG1) family. Using biochemical, structural, genetic, and pharmacological approaches across evolutionarily divergent models, including zebrafish and mice, we demonstrate a critical role for ZNG1 proteins in regulating cellular Zn homeostasis. Collectively, these data reveal the existence of a family of Zn metallochaperones and assign ZNG1 an important role for intracellular Zn trafficking.
Topics: Animals; GTP Phosphohydrolases; Homeostasis; Metallochaperones; Metalloendopeptidases; Metalloproteins; Mice; Zebrafish; Zinc
PubMed: 35584702
DOI: 10.1016/j.cell.2022.04.011 -
Metallomics : Integrated Biometal... Feb 2019
Topics: Animals; Female; History, 20th Century; History, 21st Century; Humans; Male; Metalloproteins; Metallothionein; Research Personnel
PubMed: 30648717
DOI: 10.1039/c8mt90046a -
Metallomics : Integrated Biometal... Jun 2019Biological trace metals are needed by all living organisms in very small quantities. They play important roles in a variety of key cellular processes, resulting in a... (Review)
Review
Biological trace metals are needed by all living organisms in very small quantities. They play important roles in a variety of key cellular processes, resulting in a varying degree of dependence on metals for different organisms. While most effort has been placed on identifying metal metabolic pathways and characterizing metalloproteins and their functions, computational and systematical analyses of the metallomes (or metalloproteomes) have been limited. In the past several years, comparative genomics of the metallomes has arisen, which provides significant insights into the metabolism and function of metals as well as their evolution. This review focuses on recent progress in comparative genomic analysis of trace metals (such as copper, molybdenum, nickel, cobalt, selenium, iron and zinc) in both prokaryotes and eukaryotes. These studies reveal distinct and dynamic evolutionary patterns of the utilization of different metals and metalloproteins. We also discuss advances in comparative metagenomic analysis of metals in microbial communities in diverse environments such as the global marine ecosystem, which offer new clues to the relationship between metal utilization and different types of environmental factors. Overall, comparative genomic and metagenomic analyses of the metallomes provide a foundation for systematic understanding of metal utilization, function and related evolutionary trends in the three domains of life.
Topics: Animals; Biological Evolution; Genomics; Humans; Metagenomics; Metalloproteins; Metals; Microbiota; Trace Elements
PubMed: 31021335
DOI: 10.1039/c9mt00023b -
Accounts of Chemical Research Mar 2019Many artificial enzymes that catalyze redox reactions have important energy, environmental, and medical applications. Native metalloenzymes use a set of redox-active... (Review)
Review
Many artificial enzymes that catalyze redox reactions have important energy, environmental, and medical applications. Native metalloenzymes use a set of redox-active amino acids and cofactors as redox centers, with a potential range between -700 and +800 mV versus standard hydrogen electrode (SHE, all reduction potentials are versus SHE). The redox potentials and the orientation of redox centers in native metalloproteins are optimal for their redox chemistry. However, the limited number and potential range of native redox centers challenge the design and optimization of novel redox chemistry in metalloenzymes. Artificial metalloenzymes use non-native redox centers and could go far beyond the natural range of redox potentials for novel redox chemistry. In addition to designing protein monomers, strategies for increasing the electron transfer rate in self-assembled protein complexes and protein-electrode or -nanomaterial interfaces will be discussed. Redox reactions in proteins occur on redox active amino acid residues (Tyr, Trp, Met, Cys, etc.) and cofactors (iron sulfur clusters, flavin, heme, etc.). The redox potential of these redox centers cover a ∼1.5 V range and is optimized for their specific functions. Despite recent progress, tuning the redox potential for amino acid residues or cofactors remains challenging. Many redox-active unnatural amino acids (UAAs) can be incorporated into protein via genetic codon expansion. Their redox potentials extend the range of physiologically relevant potentials. Indeed, installing new redox cofactors with fined-tuned redox potentials is essential for designing novel redox enzymes. By combining UAA and redox cofactor incorporation, we harnessed light energy to reduce CO in a fluorescent protein, mimicking photosynthetic apparatus in nature. Manipulating the position and reduction potential of redox centers inside proteins is important for optimizing the electron transfer rate and the activity of artificial enzymes. Learning from the native electron transfer complex, protein-protein interactions can be enhanced by increasing the electrostatic interaction between proteins. An artificial oxidase showed close to native enzyme activity with optimized interaction with electron transfer partner and increased electron transfer efficiency. In addition to the de novo design of protein-protein interaction, protein self-assembly methods using scaffolds, such as proliferating cell nuclear antigen, to efficiently anchor enzymes and their redox partners. The self-assembly process enhances electron transfer efficiency and enzyme activity by bringing redox centers into close proximity of each other. In addition to protein self-assembly, protein-electrode or protein-nanomaterial self-assembly can also promote efficient electron transfer from inorganic materials to enzyme active sites. Such hybrid systems combine the efficiency of enzyme reactions and the robustness of electrodes or nanomaterials, often with advantageous catalytic activities. By combining these strategies, we can not only mimic some of nature's most fascinating reactions, such as photosynthesis and aerobic respiration, but also transcend nature toward environmental, energy, and health applications.
Topics: Catalysis; Coenzymes; Electron Transport; Metalloproteins; Oxidation-Reduction; Photosynthesis; Protein Engineering
PubMed: 30816694
DOI: 10.1021/acs.accounts.8b00627 -
Colloids and Surfaces. B, Biointerfaces Oct 2022Much research has been done on traditional homogeneous metal catalysts and enzymatic catalysts, but recently a new class of hybrid catalysts called synthetic... (Review)
Review
Much research has been done on traditional homogeneous metal catalysts and enzymatic catalysts, but recently a new class of hybrid catalysts called synthetic (artificial) metalloenzymes has been considered by researchers. Metalloenzymes as hybrid catalysts (host-guest systems) have been shown that combine the properties of a homogeneous and also enzymatic catalyst. The hybrid catalyst will have added value such as enantioselectivity or chemo-selectivity. This review focuses on Schiff base complexes that either act as homogeneous artificial enzymes or contribute to the structure of a host in the preparation of hybrid metalloenzymes. Because this approach can virtually be applied to any bio- or synthetic host or guest coordination complex, the details of hybrid catalysts seem important for advance in catalysis.
Topics: Catalysis; Metalloproteins; Schiff Bases
PubMed: 35921691
DOI: 10.1016/j.colsurfb.2022.112727 -
Advances in Microbial Physiology 2017
Topics: Anti-Infective Agents; Bacterial Physiological Phenomena; Homeostasis; Ion Transport; Ions; Metalloproteins; Metals
PubMed: 28528653
DOI: 10.1016/S0065-2911(17)30018-8 -
Current Opinion in Chemical Biology Apr 2021Metal ions play an important role in diverse biological processes, and much of the basic knowledge derived from studying native bioinorganic systems are applied in the... (Review)
Review
Metal ions play an important role in diverse biological processes, and much of the basic knowledge derived from studying native bioinorganic systems are applied in the synthesis of new molecules with the aim of diagnosing and treating diseases. At first glance, metalloproteins and metallodrugs are very different systems, but metal ion coordination, redox chemistry and substrate binding play essential roles in advancing both of these research fields. In this article, we discuss recent metalloprotein and metallodrug studies where electron paramagnetic resonance spectroscopy served as a major tool to gain a better understanding of metal-based structures and their function.
Topics: Electron Spin Resonance Spectroscopy; Humans; Metalloproteins; Protein Conformation
PubMed: 33422836
DOI: 10.1016/j.cbpa.2020.11.005 -
The Biochemical Journal Apr 2015Calcineurin-like metallophosphoesterases (MPEs) form a large superfamily of binuclear metal-ion-centre-containing enzymes that hydrolyse phosphomono-, phosphodi- or... (Review)
Review
Calcineurin-like metallophosphoesterases (MPEs) form a large superfamily of binuclear metal-ion-centre-containing enzymes that hydrolyse phosphomono-, phosphodi- or phosphotri-esters in a metal-dependent manner. The MPE domain is found in Mre11/SbcD DNA-repair enzymes, mammalian phosphoprotein phosphatases, acid sphingomyelinases, purple acid phosphatases, nucleotidases and bacterial cyclic nucleotide phosphodiesterases. Despite this functional diversity, MPEs show a remarkably similar structural fold and active-site architecture. In the present review, we summarize the available structural, biochemical and functional information on these proteins. We also describe how diversification and specialization of the core MPE fold in various MPEs is achieved by amino acid substitution in their active sites, metal ions and regulatory effects of accessory domains. Finally, we discuss emerging roles of these proteins as non-catalytic protein-interaction scaffolds. Thus we view the MPE superfamily as a set of proteins with a highly conserved structural core that allows embellishment to result in dramatic and niche-specific diversification of function.
Topics: Animals; Catalytic Domain; DNA Repair; DNA-Binding Proteins; Exonucleases; Humans; MRE11 Homologue Protein; Metalloproteins; Protein Folding; Structure-Activity Relationship
PubMed: 25837850
DOI: 10.1042/BJ20150028 -
Chemical Society Reviews Sep 2014More than one third of all proteins are metalloproteins. They catalyze important reactions such as photosynthesis, nitrogen fixation and CO2 reduction. Metalloproteins... (Review)
Review
More than one third of all proteins are metalloproteins. They catalyze important reactions such as photosynthesis, nitrogen fixation and CO2 reduction. Metalloproteins such as the olfactory receptors also serve as highly elaborate sensors. Here we review recent developments in functional metalloprotein design using the genetic code expansion approach. We show that, through the site-specific incorporation of metal-chelating unnatural amino acids (UAAs), proton and electron transfer mediators, and UAAs bearing bioorthogonal reaction groups, small soluble proteins can recapitulate and expand the important functions of complex metalloproteins. Further developments along this route may result in cell factories and live-cell sensors with unprecedented efficiency and selectivity.
Topics: Amino Acids; Catalytic Domain; Chelating Agents; Genetic Code; Hemeproteins; Metalloproteins; Photosystem II Protein Complex; Porphyrins
PubMed: 24699759
DOI: 10.1039/c4cs00018h