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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 -
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 -
Dalton Transactions (Cambridge, England... Mar 2022The amino acid residue methionine (Met) is commonly thought of as a ligand in redox metalloproteins, for example in cytochromes and in blue copper proteins. However,... (Review)
Review
The amino acid residue methionine (Met) is commonly thought of as a ligand in redox metalloproteins, for example in cytochromes and in blue copper proteins. However, the roles of Met can go beyond a simple ligand. The thioether functional group of Met allows it to be considered as a hydrophobic residue as well as one that is capable of weak dipolar interactions. In addition, the lone pairs on sulphur allow Met to interact with other groups, inluding the aforementioned metal ions. Because of its properties, Met can play diverse roles in metal coordination, fine tuning of redox reactions, or supporting protein structures. These roles are strongly influenced by the nature of the surrounding medium. Herein, we describe several common interactions between Met and surrounding aromatic amino acids and how they affect the physical properties of both copper and iron metalloproteins. While the importance of interactions between Met and other groups is established in biological systems, less is known about their roles in redox metalloproteins and our view is that this is an area that is ready for greater attention.
Topics: Copper; Metalloproteins; Methionine; Models, Molecular; Oxidation-Reduction
PubMed: 35253809
DOI: 10.1039/d1dt04387k -
Metallomics : Integrated Biometal... Jul 2022Metals play a critical role in human health and diseases. In recent years, metallomics has been introduced and extensively applied to investigate the distribution,... (Review)
Review
Metals play a critical role in human health and diseases. In recent years, metallomics has been introduced and extensively applied to investigate the distribution, regulation, function, and crosstalk of metal(loid) ions in various physiological and pathological processes. Based on high-throughput multielemental analytical techniques and bioinformatics methods, it is possible to elucidate the correlation between the metabolism and homeostasis of diverse metals and complex diseases, in particular for cancer. This review aims to provide an overview of recent progress made in the application of metallomics in cancer research. We mainly focuses on the studies about metallomic profiling of different human biological samples for several major types of cancer, which reveal distinct and dynamic patterns of metal ion contents and the potential benefits of using such information in the detection and prognosis of these malignancies. Elevated levels of copper appear to be a significant risk factor for various cancers, and each type of cancer has a unique distribution of metals in biofluids, hair/nails, and tumor-affected tissues. Furthermore, associations between genetic variations in representative metalloprotein genes and cancer susceptibility have also been demonstrated. Overall, metallomics not only offers a better understanding of the relationship between metal dyshomeostasis and the development of cancer but also facilitates the discovery of new diagnostic and prognostic markers for cancer translational medicine.
Topics: Copper; Humans; Metalloproteins; Metals; Neoplasms; Prognosis
PubMed: 35648480
DOI: 10.1093/mtomcs/mfac037 -
International Journal of Molecular... Aug 2020Carbonic anhydrases (CAs) and metallothioneins (MTs) are both families of zinc metalloproteins central to life, however, they coordinate and interact with their Zn ion... (Review)
Review
Carbonic anhydrases (CAs) and metallothioneins (MTs) are both families of zinc metalloproteins central to life, however, they coordinate and interact with their Zn ion cofactors in completely different ways. CAs and MTs are highly sensitive to the cellular environment and play key roles in maintaining cellular homeostasis. In addition, CAs and MTs have multiple isoforms with differentiated regulation. This review discusses current literature regarding these two families of metalloproteins in carcinogenesis, with a dialogue on the association of these two ubiquitous proteins in vitro in the context of metalation. Metalation of CA by Zn-MT and Cd-MT is described. Evidence for protein-protein interactions is introduced from changes in metalation profiles of MT from electrospray ionization mass spectrometry and the metalation rate from stopped-flow kinetics. The implications on cellular control of pH and metal donation is also discussed in the context of diseased states.
Topics: Animals; Cadmium; Carbonic Anhydrases; Humans; Metalloproteins; Metallothionein; Metals; Models, Molecular; Protein Binding; Protein Conformation; Spectrometry, Mass, Electrospray Ionization; Zinc
PubMed: 32784815
DOI: 10.3390/ijms21165697 -
International Journal of Molecular... Jul 2022All living organisms require metal ions for their energy production and metabolic and biosynthetic processes. Within cells, the metal ions involved in the formation of... (Review)
Review
All living organisms require metal ions for their energy production and metabolic and biosynthetic processes. Within cells, the metal ions involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions in order to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted by the successful applications of neural networks and machine/deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of the methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarizing recent ML/DL applications enhancing the functional interpretation of metalloprotein structures.
Topics: Binding Sites; Computational Biology; Databases, Protein; Deep Learning; Metalloproteins; Metals
PubMed: 35887033
DOI: 10.3390/ijms23147684 -
Chemistry, An Asian Journal May 2022Waning resources, massive energy consumption, ever-deepening global warming crisis, and climate change have raised grave concerns regarding continued dependence on... (Review)
Review
Waning resources, massive energy consumption, ever-deepening global warming crisis, and climate change have raised grave concerns regarding continued dependence on fossil fuels as the predominant source of energy and generated tremendous interest for developing biofuels, which are renewable. Hydrocarbon-based 'drop-in' biofuels can be a proper substitute for fossil fuels such as gasoline or jet fuel. In Nature, hydrocarbons are produced by diverse organisms such as insects, plants, bacteria, and cyanobacteria. Metalloenzymes play a crucial role in hydrocarbons biosynthesis, and the past decade has witnessed discoveries of a number of metalloenzymes catalyzing hydrocarbon biosynthesis from fatty acids and their derivatives employing unprecedented mechanisms. These discoveries elucidated the enigma related to the divergent chemistries involved in the catalytic mechanisms of these metalloenzymes. There is substantial diversity in the structure, mode of action, cofactor requirement, and substrate scope among these metalloenzymes. Detailed structural analysis along with mutational studies of some of these enzymes have contributed significantly to identifying the key amino acid residues that dictate substrate specificity and catalytic intricacy. In this Review, we discuss the metalloenzymes that catalyze fatty acid-derived hydrocarbon biosynthesis in various organisms, emphasizing the active site architecture, catalytic mechanism, cofactor requirements, and substrate specificity of these enzymes. Understanding such details is essential for successfully implementing these enzymes in emergent biofuel research through protein engineering and synthetic biology approaches.
Topics: Biofuels; Fatty Acids; Fossil Fuels; Hydrocarbons; Metalloproteins
PubMed: 35319822
DOI: 10.1002/asia.202200105 -
Chemical Communications (Cambridge,... Aug 2020By combining synthetic catalysts and biochemical tools, numerous artificial metalloenzymes have been designed to exhibit high catalytic activity and selectivity in... (Review)
Review
By combining synthetic catalysts and biochemical tools, numerous artificial metalloenzymes have been designed to exhibit high catalytic activity and selectivity in diverse chemical transformations. Out of the nearly infinite number of discovered or characterised proteins, however, only a handful of proteins have been employed as scaffolds for artificial metalloenzymes, implying that specific proteins are preferred owing to their native structural, functional, or biochemical properties. In the present review, we extract and group the biochemical and structural properties of proteins that are advantageous in the design of artificial metalloenzymes; protein stability, pre-existing metal centre, native binding affinity for small molecules, confined and empty space, well-defined secondary structure, and native cellular location. The desirable properties highlight proteins as the key players in the design of metal-dependent biocatalysts. We also propose rarely considered, yet promising, proteins that could be versatile and unique scaffolds for novel metalloenzymes.
Topics: Animals; Catalytic Domain; Cysteine; Metalloproteins; Metals; Muramidase; Protein Conformation; Protein Stability
PubMed: 32691751
DOI: 10.1039/d0cc03137b -
Biotechnology and Applied Biochemistry Jul 2020Over the years, mimochromes, a class of miniaturized porphyrin-based metalloproteins, have proven to be reliable but still versatile scaffolds. After two decades from... (Review)
Review
Over the years, mimochromes, a class of miniaturized porphyrin-based metalloproteins, have proven to be reliable but still versatile scaffolds. After two decades from their birth, we retrospectively review our work in mimochrome design and engineering, which allowed us developing functional models. They act as electron-transfer miniproteins or more elaborate artificial metalloenzymes, endowed with peroxidase, peroxygenase, and hydrogenase activities. Mimochromes represent simple yet functional synthetic models that respond to metal ion replacement and noncovalent modulation of the environment, similarly to natural heme-proteins. More recently, we have demonstrated that the most active analogue retains its functionality when immobilized on nanomaterials and surfaces, thus affording bioconjugates, useful in sensing and catalysis. This review also briefly summarizes the most important contributions to heme-protein design from leading groups in the field.
Topics: Biomimetic Materials; Catalysis; Metalloporphyrins; Metalloproteins
PubMed: 32658365
DOI: 10.1002/bab.1985 -
Journal of Inorganic Biochemistry Dec 2023The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind...
The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind divalent metals with its twenty cysteines. While the two-domain structure for CdMT is well-established as a CdS and CdS, a third structure has been reported when 8 Cd(II) ions bind to MT1. Isoform 3 of the MT family, MT3, has been of interest to the research community since its isolation as a growth inhibitory factor isolated in brain tissue, and has since been noted as a prominent participant in the mediation of neurodegenerative diseases and regular brain development. The differences between MT3 and the other isoforms of MT include an additional hexapeptide insertion of acidic residues in the α domain as well as the introduction of two prolines in the β domain. It is unclear whether these changes impact the metalation properties of MT3. We report the formation of a CdMT3 species is characterized by electrospray ionization mass spectrometry and UV-visible absorption spectroscopy. We report that the spectroscopic properties of this supermetalated CdMT3 are similar to those of the supermetalated CdMT1, with a clear indication of changes in structure from "fully-metalated" CdMT3 to supermetalated CdMT3 from circular dichroism spectra and both 1D Cd and 2D H-Cd HSQC NMR spectra. We conclude that the metalation properties are not impacted significantly due to the amino acid changes in MT3, and that the cysteinyl thiols are the key players in determining the capacity of metal-binding and the structure of metal-thiolate clusters.
Topics: Humans; Animals; Metallothionein 3; Cadmium; Metals; Metallothionein; Circular Dichroism; Mammals
PubMed: 37832463
DOI: 10.1016/j.jinorgbio.2023.112392