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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 -
FEBS Letters Apr 2013Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both... (Review)
Review
Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications.
Topics: Contrast Media; Ferrosoferric Oxide; Image Enhancement; Magnetic Resonance Imaging; Metalloproteins; Models, Chemical; Models, Molecular; Mutation; Protein Engineering
PubMed: 23376346
DOI: 10.1016/j.febslet.2013.01.044 -
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 Structural Biology Aug 2022Metalloproteins comprise at least a third of all proteins that utilize redox properties of transition metals on their own or as parts of cofactors. The development of... (Review)
Review
Metalloproteins comprise at least a third of all proteins that utilize redox properties of transition metals on their own or as parts of cofactors. The development of third generation storage ring sources and X-ray free-electron lasers with femtosecond pulses in the first decade of the 21st century has transformed metalloprotein crystallography. In the past decade, cryogenic-electron microscopy single-particle analysis, which does not require crystallization of biological samples has been extensively utilized, particularly for membrane-bound metalloprotein systems. Here, we explore recent frontiers in metalloprotein crystallography and cryogenic electron microscopy, organized for convenience under three metalloprotein-centered biological cycles, focusing on contributions from each technique, their synergy and the ability to preserve metals' redox states when subjected to a particular probe.
Topics: Cryoelectron Microscopy; Crystallization; Crystallography; Crystallography, X-Ray; Metalloproteins; X-Rays
PubMed: 35841747
DOI: 10.1016/j.sbi.2022.102420 -
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 -
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 -
Current Opinion in Biotechnology Aug 1996The rational design of novel proteins offers a new method of studying structure and function, and makes possible the construction of new biomaterials. The richness of... (Review)
Review
The rational design of novel proteins offers a new method of studying structure and function, and makes possible the construction of new biomaterials. The richness of metal chemistry, the relative ease of creating stable complexes, and the remarkable degree of subtle, highly specific control of reactivity imposed by the protein matrix upon the metal center make metalloprotein design a very fruitful area for the exploration and application of design techniques. So far, most designs have concentrated on the exploration of simple metal-chelation properties. Even so, this has led to the development of new methods for protein stabilization and affinity purification, of metal biosensors, of novel strategies for control of protein activity, and of model systems for the exploration of fundamental principles of molecular recognition.
Topics: Binding Sites; Biosensing Techniques; Forecasting; Metalloproteins; Metals; Protein Conformation; Protein Engineering; Structure-Activity Relationship
PubMed: 8768904
DOI: 10.1016/s0958-1669(96)80121-2 -
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 -
International Journal of Molecular... Feb 2022Cadmium (Cd) pollution in cultivated land is caused by irresistible geological factors and human activities; intense diffusion and migration have seriously affected the... (Review)
Review
Cadmium (Cd) pollution in cultivated land is caused by irresistible geological factors and human activities; intense diffusion and migration have seriously affected the safety of food crops. Plants have evolved mechanisms to control excessive influx of Cd in the environment, such as directional transport, chelation and detoxification. This is done by some specific metalloproteins, whose key amino acid motifs have been investigated by scientists one by one. The application of powerful cell biology, crystal structure science, and molecular probe targeted labeling technology has identified a series of protein families involved in the influx, transport and detoxification of the heavy metal Cd. This review summarizes them as influx proteins (NRAMP, ZIP), chelating proteins (MT, PDF), vacuolar proteins (CAX, ABCC, MTP), long-distance transport proteins (OPT, HMA) and efflux proteins (PCR, ABCG). We selected representative proteins from each family, and compared their amino acid sequence, motif structure, subcellular location, tissue specific distribution and other characteristics of differences and common points, so as to summarize the key residues of the Cd binding target. Then, we explain its special mechanism of action from the molecular structure. In conclusion, this review is expected to provide a reference for the exploration of key amino acid targets of Cd, and lay a foundation for the intelligent design and breeding of crops with high/low Cd accumulation.
Topics: Amino Acids; Cadmium; Inactivation, Metabolic; Metalloproteins; Plants; Stress, Physiological
PubMed: 35163656
DOI: 10.3390/ijms23031734 -
Trends in Biochemical Sciences Dec 2019Metalloproteins are crucial for life. The mutual relationship between metal ions and proteins makes metalloproteins able to accomplish key processes in biological... (Review)
Review
Metalloproteins are crucial for life. The mutual relationship between metal ions and proteins makes metalloproteins able to accomplish key processes in biological systems, often very difficult to reproduce with inorganic coordination compounds under mild conditions. Taking inspiration from nature, many efforts have been devoted to developing artificial molecules as metalloprotein mimics. We have witnessed an explosion of protein design strategies leading to designed metalloproteins, ranging from stable structures to functional molecules. This review illustrates the most recent results for inserting metalloprotein functions in designed and engineered protein scaffolds. The selected examples highlight the potential of different approaches for the construction of artificial molecules capable of simulating and even overcoming the features of natural metalloproteins.
Topics: Metalloproteins; Protein Engineering
PubMed: 31307903
DOI: 10.1016/j.tibs.2019.06.006