-
Molecules (Basel, Switzerland) Jul 2019Metalloproteins and metalloenzymes play important roles in biological systems by using the limited metal ions, complexes, and clusters that are associated with the... (Review)
Review
Metalloproteins and metalloenzymes play important roles in biological systems by using the limited metal ions, complexes, and clusters that are associated with the protein matrix. The design of artificial metalloproteins and metalloenzymes not only reveals the structure and function relationship of natural proteins, but also enables the synthesis of artificial proteins and enzymes with improved properties and functions. Acknowledging the progress in rational design from single to multiple active sites, this review focuses on recent achievements in the design of artificial metalloproteins and metalloenzymes with metal clusters, including zinc clusters, cadmium clusters, iron-sulfur clusters, and copper-sulfur clusters, as well as noble metal clusters and others. These metal clusters were designed in both native and de novo protein scaffolds for structural roles, electron transfer, or catalysis. Some synthetic metal clusters as functional models of native enzymes are also discussed. These achievements provide valuable insights for deep understanding of the natural proteins and enzymes, and practical clues for the further design of artificial enzymes with functions comparable or even beyond those of natural counterparts.
Topics: Carrier Proteins; Catalysis; Catalytic Domain; Enzymes; Metalloproteins; Metals; Models, Molecular; Molecular Conformation; Molecular Structure; Protein Binding; Protein Engineering
PubMed: 31362341
DOI: 10.3390/molecules24152743 -
Acta Crystallographica. Section D,... Oct 2021Metalloproteins catalyze a range of reactions, with enhanced chemical functionality due to their metal cofactor. The reaction mechanisms of metalloproteins have been... (Review)
Review
Metalloproteins catalyze a range of reactions, with enhanced chemical functionality due to their metal cofactor. The reaction mechanisms of metalloproteins have been experimentally characterized by spectroscopy, macromolecular crystallography and cryo-electron microscopy. An important caveat in structural studies of metalloproteins remains the artefacts that can be introduced by radiation damage. Photoreduction, radiolysis and ionization deriving from the electromagnetic beam used to probe the structure complicate structural and mechanistic interpretation. Neutron protein diffraction remains the only structural probe that leaves protein samples devoid of radiation damage, even when data are collected at room temperature. Additionally, neutron protein crystallography provides information on the positions of light atoms such as hydrogen and deuterium, allowing the characterization of protonation states and hydrogen-bonding networks. Neutron protein crystallography has further been used in conjunction with experimental and computational techniques to gain insight into the structures and reaction mechanisms of several transition-state metal oxidoreductases with iron, copper and manganese cofactors. Here, the contribution of neutron protein crystallography towards elucidating the reaction mechanism of metalloproteins is reviewed.
Topics: Animals; Catalysis; Crystallography, X-Ray; Humans; Metalloproteins; Models, Molecular; Neutron Diffraction; Neutrons; Oxidoreductases
PubMed: 34605429
DOI: 10.1107/S2059798321009025 -
Current Opinion in Chemical Biology Apr 2015This review presents recent examples of metal-binding promiscuity in protein scaffolds and highlights the effect of metal variation on catalytic functionality. Naturally... (Review)
Review
This review presents recent examples of metal-binding promiscuity in protein scaffolds and highlights the effect of metal variation on catalytic functionality. Naturally evolved binding sites, as well as unnatural amino acids and cofactors can bind a diverse range of metals, including non-biological transition elements. Computational screening and rational design have been successfully used to create promiscuous binding-sites. Incorporation of non-native metals into proteins expands the catalytic range of transformations catalysed by enzymes and enhances their potential for application in chemicals synthesis.
Topics: Amino Acids; Enzymes; Metalloproteins; Metals; Protein Engineering; Substrate Specificity
PubMed: 25603469
DOI: 10.1016/j.cbpa.2014.12.035 -
Chemical Society Reviews Sep 2016Many efforts are being made in the design and engineering of metalloenzymes with catalytic properties fulfilling the needs of practical applications. Progress in this... (Review)
Review
Many efforts are being made in the design and engineering of metalloenzymes with catalytic properties fulfilling the needs of practical applications. Progress in this field has recently been accelerated by advances in computational, molecular and structural biology. This review article focuses on the recent examples of oxygen-activating metalloenzymes, developed through the strategies of de novo design, miniaturization processes and protein redesign. Considerable progress in these diverse design approaches has produced many metal-containing biocatalysts able to adopt the functions of native enzymes or even novel functions beyond those found in Nature.
Topics: Enzyme Activation; Metalloproteins; Oxygen; Oxygenases; Protein Engineering
PubMed: 27341693
DOI: 10.1039/c5cs00923e -
Genomics, Proteomics & Bioinformatics Dec 2021Trace elements are required by all organisms, which are key components of many enzymes catalyzing important biological reactions. Many trace element-dependent proteins...
Trace elements are required by all organisms, which are key components of many enzymes catalyzing important biological reactions. Many trace element-dependent proteins have been characterized; however, little is known about their occurrence in microbial communities in diverse environments, especially the global marine ecosystem. Moreover, the relationships between trace element utilization and different types of environmental stressors are unclear. In this study, we used metagenomic data from the Global Ocean Sampling expedition project to identify the biogeographic distribution of genes encoding trace element-dependent proteins (for copper, molybdenum, cobalt, nickel, and selenium) in a variety of marine and non-marine aquatic samples. More than 56,000 metalloprotein and selenoprotein genes corresponding to nearly 100 families were predicted, becoming the largest dataset of marine metalloprotein and selenoprotein genes reported to date. In addition, samples with enriched or depleted metalloprotein/selenoprotein genes were identified, suggesting an active or inactive usage of these micronutrients in various sites. Further analysis of interactions among the elements showed significant correlations between some of them, especially those between nickel and selenium/copper. Finally, investigation of the relationships between environmental conditions and metalloprotein/selenoprotein families revealed that many environmental factors might contribute to the evolution of different metalloprotein and/or selenoprotein genes in the marine microbial world. Our data provide new insights into the utilization and biological roles of these trace elements in extant marine microbes, and might also be helpful for the understanding of how these organisms have adapted to their local environments.
Topics: Copper; Metalloproteins; Microbiota; Nickel; Seawater; Selenium; Selenoproteins; Trace Elements; Water Microbiology
PubMed: 33631428
DOI: 10.1016/j.gpb.2021.02.003 -
International Journal of Molecular... Jul 2019Dimethyl sulfoxide reductases (DMSO) are molybdoenzymes widespread in all domains of life. They catalyse not only redox reactions, but also hydroxylation/hydration and... (Review)
Review
Dimethyl sulfoxide reductases (DMSO) are molybdoenzymes widespread in all domains of life. They catalyse not only redox reactions, but also hydroxylation/hydration and oxygen transfer processes. Although literature on DMSO is abundant, the biological significance of these enzymes in anaerobic respiration and the molecular mechanisms beyond the expression of genes coding for them are still scarce. In this review, a deep revision of the literature reported on DMSO as well as the use of bioinformatics tools and free software has been developed in order to highlight the relevance of DMSO reductases on anaerobic processes connected to different biogeochemical cycles. Special emphasis has been addressed to DMSO from extremophilic organisms and their role in nitrogen cycle. Besides, an updated overview of phylogeny of DMSOs as well as potential applications of some DMSO reductases on bioremediation approaches are also described.
Topics: Coenzymes; Extremophiles; Iron-Sulfur Proteins; Isoenzymes; Metabolic Networks and Pathways; Metalloproteins; Molybdenum; Molybdenum Cofactors; Multigene Family; Nitrogen Cycle; Oxidation-Reduction; Oxidoreductases; Phylogeny; Pteridines; Structure-Activity Relationship; Tungsten
PubMed: 31288391
DOI: 10.3390/ijms20133349 -
Biomolecules Mar 2022Metalloproteins are involved in key cell processes such as photosynthesis, respiration, and oxygen transport. However, the presence of transition metals (notably iron as...
Metalloproteins are involved in key cell processes such as photosynthesis, respiration, and oxygen transport. However, the presence of transition metals (notably iron as a component of [Fe-S] clusters) often makes these proteins sensitive to oxygen-induced degradation. Consequently, their study usually requires strict anaerobic conditions. Although X-ray crystallography has been the method of choice for solving macromolecular structures for many years, recently electron microscopy has also become an increasingly powerful structure-solving technique. We have used our previous experience with cryo-crystallography to develop a method to prepare cryo-EM grids in an anaerobic chamber and have applied it to solve the structures of apoferritin and the 3 [FeS]-containing pyruvate ferredoxin oxidoreductase (PFOR) at 2.40 Å and 2.90 Å resolution, respectively. The maps are of similar quality to the ones obtained under air, thereby validating our method as an improvement in the structural investigation of oxygen-sensitive metalloproteins by cryo-EM.
Topics: Apoferritins; Cryoelectron Microscopy; Crystallography, X-Ray; Metalloproteins; Oxygen
PubMed: 35327633
DOI: 10.3390/biom12030441 -
Methods in Enzymology 2016Heteronuclear metalloenzymes catalyze some of the most fundamentally interesting and practically useful reactions in nature. However, the presence of two or more metal...
Heteronuclear metalloenzymes catalyze some of the most fundamentally interesting and practically useful reactions in nature. However, the presence of two or more metal ions in close proximity in these enzymes makes them more difficult to prepare and study than homonuclear metalloenzymes. To meet these challenges, heteronuclear metal centers have been designed into small and stable proteins with rigid scaffolds to understand how these heteronuclear centers are constructed and the mechanism of their function. This chapter describes methods for designing heterobinuclear metal centers in a protein scaffold by giving specific examples of a few heme-nonheme bimetallic centers engineered in myoglobin and cytochrome c peroxidase. We provide step-by-step procedures on how to choose the protein scaffold, design a heterobinuclear metal center in the protein scaffold computationally, incorporate metal ions into the protein, and characterize the resulting metalloproteins, both structurally and functionally. Finally, we discuss how an initial design can be further improved by rationally tuning its secondary coordination sphere, electron/proton transfer rates, and the substrate affinity.
Topics: Catalysis; Cytochrome-c Peroxidase; Heme; Ions; Metalloproteins; Metals; Myoglobin; Oxidation-Reduction; Protein Engineering
PubMed: 27586347
DOI: 10.1016/bs.mie.2016.05.050 -
Biochimica Et Biophysica Acta May 2016Iron-sulfur centers in metalloproteins can access multiple oxidation states over a broad range of potentials, allowing them to participate in a variety of electron... (Review)
Review
Iron-sulfur centers in metalloproteins can access multiple oxidation states over a broad range of potentials, allowing them to participate in a variety of electron transfer reactions and serving as catalysts for high-energy redox processes. The nitrogenase FeMoCO cluster converts di-nitrogen to ammonia in an eight-electron transfer step. The 2(Fe4S4) containing bacterial ferredoxin is an evolutionarily ancient metalloprotein fold and is thought to be a primordial progenitor of extant oxidoreductases. Controlling chemical transformations mediated by iron-sulfur centers such as nitrogen fixation, hydrogen production as well as electron transfer reactions involved in photosynthesis are of tremendous importance for sustainable chemistry and energy production initiatives. As such, there is significant interest in the design of iron-sulfur proteins as minimal models to gain fundamental understanding of complex natural systems and as lead-molecules for industrial and energy applications. Herein, we discuss salient structural characteristics of natural iron-sulfur proteins and how they guide principles for design. Model structures of past designs are analyzed in the context of these principles and potential directions for enhanced designs are presented, and new areas of iron-sulfur protein design are proposed. This article is part of a Special issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, protein networks, edited by Ronald L. Koder and J.L Ross Anderson.
Topics: Catalytic Domain; Computational Biology; Ferredoxins; Iron; Iron-Sulfur Proteins; Metalloproteins; Models, Molecular; Protein Engineering; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Sulfur
PubMed: 26449207
DOI: 10.1016/j.bbabio.2015.10.001 -
Chemical Communications (Cambridge,... Dec 2020Bioinspired transformation of small-molecules to energy-related feedstocks is an attractive research area to overcome both the environmental issues and the depletion of... (Review)
Review
Bioinspired transformation of small-molecules to energy-related feedstocks is an attractive research area to overcome both the environmental issues and the depletion of fossil fuels. The highly effective metalloenzymes in nature provide blueprints for the utilization of bioinspired metal complexes for artificial photosynthesis. Through simpler structural and functional mimics, the representative herein is the pivotal development of several critical small molecule conversions catalyzed by metal complexes, e.g., water oxidation, proton and CO reduction and organic chemical transformation of small molecules. Of great achievement is the establishment of bioinspired metal complexes as catalysts with high stability, specific selectivity and satisfactory efficiency to drive the multiple-electron and multiple-proton processes related to small molecule transformation. Also, potential opportunities and challenges for future development in these appealing areas are highlighted.
Topics: Catalysis; Coordination Complexes; Metalloproteins; Photochemical Processes; Small Molecule Libraries
PubMed: 33300513
DOI: 10.1039/d0cc05870j