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FEBS Letters Jan 2023Metalation, the acquisition of metals by proteins, must avoid mis-metalation with tighter binding metals. This is illustrated by four selected proteins that require... (Review)
Review
Metalation, the acquisition of metals by proteins, must avoid mis-metalation with tighter binding metals. This is illustrated by four selected proteins that require different metals: all show similar ranked orders of affinity for bioavailable metals, as described in a universal affinity series (the Irving-Williams series). Crucially, cellular protein metalation occurs in competition with other metal binding sites. The strength of this competition defines the intracellular availability of each metal: its magnitude has been estimated by calibrating a cells' set of DNA-binding, metal-sensing, transcriptional regulators. This has established that metal availabilities (as free energies for forming metal complexes) are maintained to the inverse of the universal series. The tightest binding metals are least available. With these availabilities, correct metalation is achieved.
Topics: Metals; Metalloproteins; Bacterial Proteins; Cobalt; Copper
PubMed: 36124565
DOI: 10.1002/1873-3468.14500 -
Molecules (Basel, Switzerland) Jul 2023Mo/W-containing formate dehydrogenases (FDH) catalyzes the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. The... (Review)
Review
Mo/W-containing formate dehydrogenases (FDH) catalyzes the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. The metal-containing FDHs are members of the dimethylsulfoxide reductase family of mononuclear molybdenum cofactor (Moco)- or tungsten cofactor (Wco)-containing enzymes. In these enzymes, the active site in the oxidized state comprises a Mo or W atom present in the bis-Moco, which is coordinated by the two dithiolene groups from the two MGD moieties, a protein-derived SeCys or Cys, and a sixth ligand that is now accepted as being a sulfido group. SeCys-containing enzymes have a generally higher turnover number than Cys-containing enzymes. The analogous chemical properties of W and Mo, the similar active sites of W- and Mo-containing enzymes, and the fact that W can replace Mo in some enzymes have led to the conclusion that Mo- and W-containing FDHs have the same reaction mechanism. Details of the catalytic mechanism of metal-containing formate dehydrogenases are still not completely understood and have been discussed here.
Topics: Formate Dehydrogenases; Oxidation-Reduction; Metalloproteins; Molybdenum; Catalytic Domain; Pteridines; Coenzymes
PubMed: 37513211
DOI: 10.3390/molecules28145338 -
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 -
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 -
Molecules (Basel, Switzerland) Aug 2022For most organisms molybdenum is essential for life as it is found in the active site of various vitally important molybdenum dependent enzymes (Mo-enzymes). Here,... (Review)
Review
For most organisms molybdenum is essential for life as it is found in the active site of various vitally important molybdenum dependent enzymes (Mo-enzymes). Here, molybdenum is bound to a pterin derivative called molybdopterin (MPT), thus forming the molybdenum cofactor (Moco). Synthesis of Moco involves the consecutive action of numerous enzymatic reaction steps, whereby molybdenum insertases (Mo-insertases) catalyze the final maturation step, i.e., the metal insertion reaction yielding Moco. This final maturation step is subdivided into two partial reactions, each catalyzed by a distinctive Mo-insertase domain. Initially, MPT is adenylylated by the Mo-insertase G-domain, yielding MPT-AMP which is used as substrate by the E-domain. This domain catalyzes the insertion of molybdate into the MPT dithiolene moiety, leading to the formation of Moco-AMP. Finally, the Moco-AMP phosphoanhydride bond is cleaved by the E-domain to liberate Moco from its synthesizing enzyme. Thus formed, Moco is physiologically active and may be incorporated into the different Mo-enzymes or bind to carrier proteins instead.
Topics: Adenosine Monophosphate; Catalytic Domain; Coenzymes; Metalloproteins; Molybdenum; Molybdenum Cofactors; Pterins
PubMed: 36080140
DOI: 10.3390/molecules27175372 -
Nature Communications Oct 2023Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence...
Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein export and a greatly reduced level of manganese (Mn) in the secreted proteome. MeeF and MeeY copurify with proteins of the general secretory pathway, and in their absence the FtsH membrane protease is essential for viability. MeeF and MeeY are also required for efficient function of the Mn-dependent lipoteichoic acid synthase (LtaS), a membrane-localized enzyme with an extracytoplasmic active site. Thus, MeeF and MeeY, representative of the widely conserved TerC family of membrane transporters, function in the co-translocational metalation of Mn-dependent membrane and extracellular enzymes.
Topics: Bacterial Proteins; Protein Transport; Bacillus subtilis; Secretory Pathway; Metalloproteins
PubMed: 37794032
DOI: 10.1038/s41467-023-41896-1 -
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 -
International Journal of Molecular... Aug 2020Hydrogenases are complex metalloenzymes, showing tremendous potential as H-converting redox catalysts for application in light-driven H production, enzymatic fuel cells... (Review)
Review
Hydrogenases are complex metalloenzymes, showing tremendous potential as H-converting redox catalysts for application in light-driven H production, enzymatic fuel cells and H-driven cofactor regeneration. They catalyze the reversible oxidation of hydrogen into protons and electrons. The apo-enzymes are not active unless they are modified by a complicated post-translational maturation process that is responsible for the assembly and incorporation of the complex metal center. The catalytic center is usually easily inactivated by oxidation, and the separation and purification of the active protein is challenging. The understanding of the catalytic mechanisms progresses slowly, since the purification of the enzymes from their native hosts is often difficult, and in some case impossible. Over the past decades, only a limited number of studies report the homologous or heterologous production of high yields of hydrogenase. In this review, we emphasize recent discoveries that have greatly improved our understanding of microbial hydrogenases. We compare various heterologous hydrogenase production systems as well as in vitro hydrogenase maturation systems and discuss their perspectives for enhanced biohydrogen production. Additionally, activities of hydrogenases isolated from either recombinant organisms or in vivo/in vitro maturation approaches were systematically compared, and future perspectives for this research area are discussed.
Topics: Bacterial Proteins; Hydrogenase; Industrial Microbiology; Iron-Sulfur Proteins; Protein Engineering
PubMed: 32824336
DOI: 10.3390/ijms21165890 -
Journal of Inorganic Biochemistry Feb 2022Sulfide and transition metals often came together in Biology. The variety of possible structural combinations enabled living organisms to evolve an array of highly... (Review)
Review
Sulfide and transition metals often came together in Biology. The variety of possible structural combinations enabled living organisms to evolve an array of highly versatile metal-sulfide centers to fulfill different physiological roles. The ubiquitous iron‑sulfur centers, with their structural, redox, and functional diversity, are certainly the best-known partners, but other metal-sulfide centers, involving copper, nickel, molybdenum or tungsten, are equally crucial for Life. This review provides a concise overview of the exclusive sulfide properties as a metal ligand, with emphasis on the structural aspects and biosynthesis. Sulfide as catalyst and as a substrate is discussed. Different enzymes are considered, including xanthine oxidase, formate dehydrogenases, nitrogenases and carbon monoxide dehydrogenases. The sulfide effect on the activity and function of iron‑sulfur, heme and zinc proteins is also addressed.
Topics: Heme; Iron-Sulfur Proteins; Metalloproteins; Sulfides; Transition Elements
PubMed: 34953313
DOI: 10.1016/j.jinorgbio.2021.111687 -
Redox Biology Apr 2023Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in HS-mediated biological events. RSS... (Review)
Review
Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in HS-mediated biological events. RSS (including HS) can exert their biological roles via widespread interactions with metalloproteins. Metalloproteins are essential components along the metabolic route of oxygen in the body, from the transport and storage of O, through cellular respiration, to the maintenance of redox homeostasis by elimination of reactive oxygen species (ROS). Moreover, heme peroxidases contribute to immune defense by killing pathogens using oxygen-derived HO as a precursor for stronger oxidants. Coordination and redox reactions with metal centers are primary means of RSS to alter fundamental cellular functions. In addition to RSS-mediated metalloprotein functions, the reduction of high-valent metal centers by RSS results in radical formation and opens the way for subsequent per- and polysulfide formation, which may have implications in cellular protection against oxidative stress and in redox signaling. Furthermore, recent findings pointed out the potential role of RSS as substrates for mitochondrial energy production and their cytoprotective capacity, with the involvement of metalloproteins. The current review summarizes the interactions of RSS with protein metal centers and their biological implications with special emphasis on mechanistic aspects, sulfide-mediated signaling, and pathophysiological consequences. A deeper understanding of the biological actions of reactive sulfur species on a molecular level is primordial in HS-related drug development and the advancement of redox medicine.
Topics: Hydrogen Sulfide; Metalloproteins; Hydrogen Peroxide; Reactive Oxygen Species; Oxygen; Sulfur
PubMed: 36738685
DOI: 10.1016/j.redox.2023.102617