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Annual Review of Biochemistry Jun 2022Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many... (Review)
Review
Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many diseases. Metals are also frequently incorporated into diagnosis and therapeutics. Understanding of metal homeostasis under (patho)physiological conditions and the molecular mechanisms of action of metallodrugs in biological systems has positive impacts on human health. As an emerging interdisciplinary area of research, metalloproteomics involves investigating metal-protein interactions in biological systems at a proteome-wide scale, has received growing attention, and has been implemented into metal-related research. In this review, we summarize the recent advances in metalloproteomics methodologies and applications. We also highlight emerging single-cell metalloproteomics, including time-resolved inductively coupled plasma mass spectrometry, mass cytometry, and secondary ion mass spectrometry. Finally, we discuss future perspectives in metalloproteomics, aiming to attract more original research to develop more advanced methodologies, which could be utilized rapidly by biochemists or biologists to expand our knowledge of how metal functions in biology and medicine.
Topics: Biomedical Research; Humans; Metalloproteins; Metals; Proteome; Proteomics
PubMed: 35303792
DOI: 10.1146/annurev-biochem-040320-104628 -
ACS Infectious Diseases Oct 2019Gallium nitrate (Ganite) is a potential drug for the treatment of infection. CRISPR/Cas9-based gene mutagenesis studies reveal that siderophore pyochelin-facilitated...
Gallium nitrate (Ganite) is a potential drug for the treatment of infection. CRISPR/Cas9-based gene mutagenesis studies reveal that siderophore pyochelin-facilitated uptake and an ABC transporter are two major Ga internalization pathways in (). Crystal structures reveal that Ga and Fe occupy exactly the same metal site of HitA, a periplasmic iron-binding protein of the ABC transporter system. The study provides a molecular basis for Ga internalization by and facilitates gallium-based antimicrobial drug development.
Topics: ATP-Binding Cassette Transporters; Anti-Bacterial Agents; Drug Development; Gallium; Iron; Metalloproteins; Models, Molecular; Mutagenesis; Periplasm; Protein Conformation; Pseudomonas Infections; Pseudomonas aeruginosa; Siderophores
PubMed: 31475514
DOI: 10.1021/acsinfecdis.9b00271 -
Biochemical and Biophysical Research... Aug 1962
Topics: Metalloproteins; Metallothionein; Metals; Proteins
PubMed: 13923708
DOI: 10.1016/0006-291x(62)90001-3 -
Angewandte Chemie (International Ed. in... Jun 2021Metalloproteins constitute a significant fraction of the proteome of all organisms and their characterization is critical for both basic sciences and biomedical...
Metalloproteins constitute a significant fraction of the proteome of all organisms and their characterization is critical for both basic sciences and biomedical applications. A large portion of metalloproteins bind paramagnetic metal ions, and paramagnetic NMR spectroscopy has been widely used in their structural characterization. However, the signals of nuclei in the immediate vicinity of the metal center are often broadened beyond detection. In this work, we show that it is possible to determine the coordination environment of the paramagnetic metal in the protein at a resolution inaccessible to other techniques. Taking the structure of a diamagnetic analogue as a starting point, a geometry optimization is carried out by fitting the pseudocontact shifts obtained from first principles quantum chemical calculations to the experimental ones.
Topics: Magnetic Phenomena; Metalloproteins; Nuclear Magnetic Resonance, Biomolecular
PubMed: 33595173
DOI: 10.1002/anie.202101149 -
Advanced Materials (Deerfield Beach,... Nov 2022Single-atom catalysts (SACs) exhibit unparalleled atomic utilization and catalytic efficiency, yet it is challenging to modulate SACs with highly dispersed single-atoms,...
Single-atom catalysts (SACs) exhibit unparalleled atomic utilization and catalytic efficiency, yet it is challenging to modulate SACs with highly dispersed single-atoms, mesopores, and well-regulated coordination environment simultaneously and ultimately maximize their catalytic efficiency. Here, a generalized strategy to construct highly active ferric-centered SACs (Fe-SACs) is developed successfully via a biomineralization strategy that enables the homogeneous encapsulation of metalloproteins within metal-organic frameworks (MOFs) followed by pyrolysis. The results demonstrate that the constructed metalloprotein-MOF-templated Fe-SACs achieve up to 23-fold and 47-fold higher activity compared to those using metal ions as the single-atom source and those with large mesopores induced by Zn evaporation, respectively, as well as up to a 25-fold and 1900-fold higher catalytic efficiency compared to natural enzymes and natural-enzyme-immobilized MOFs. Furthermore, this strategy can be generalized to a variety of metal-containing metalloproteins and enzymes. The enhanced catalytic activity of Fe-SACs benefits from the highly dispersed atoms, mesopores, as well as the regulated coordination environment of single-atom active sites induced by metalloproteins. Furthermore, the developed Fe-SACs act as an excellent and effective therapeutic platform for suppressing tumor cell growth. This work advances the development of highly efficient SACs using metalloproteins-MOFs as a template with diverse biotechnological applications.
Topics: Metal-Organic Frameworks; Biocatalysis; Metalloproteins; Catalysis; Iron
PubMed: 36073657
DOI: 10.1002/adma.202205674 -
Marine Pollution Bulletin Nov 2020The metal detoxification mechanism is essential for the accumulation activity of some polychaetes. In order to investigate the detoxification function of metalloprotein...
The metal detoxification mechanism is essential for the accumulation activity of some polychaetes. In order to investigate the detoxification function of metalloprotein II in polychaete Perinereis aibuhitensis, a recombinant fusion protein of MP II was successfully expressed in vitro and an anti-MP II polyclonal antibody was got. The tissue distribution of MP II in P. aibuhitensis and the protein expression under Cd, Pb and Zn exposure were detected by ELISA with this antibody. The results showed that MP II was higher in the intestine of P. aibuhitensis, followed by the body wall and parapodium. Cd, Zn and Pb exposure can induced MP II expression, but the change trend of MP II under various heavy metal exposure was different. The amount of MP II induced in P. aibuhitensis increased with the rises of Cd concentration, but there is no significant relationship between Zn and Pb concentration and MP II level.
Topics: Animals; Metalloproteins; Metals, Heavy; Polychaeta
PubMed: 32889508
DOI: 10.1016/j.marpolbul.2020.111550 -
Nature Chemistry Feb 2017Engineering bioelectronic components and set-ups that mimic natural systems is extremely challenging. Here we report the design of a protein-only redox film inspired by...
Engineering bioelectronic components and set-ups that mimic natural systems is extremely challenging. Here we report the design of a protein-only redox film inspired by the architecture of bacterial electroactive biofilms. The nanowire scaffold is formed using a chimeric protein that results from the attachment of a prion domain to a rubredoxin (Rd) that acts as an electron carrier. The prion domain self-assembles into stable fibres and provides a suitable arrangement of redox metal centres in Rd to permit electron transport. This results in highly organized films, able to transport electrons over several micrometres through a network of bionanowires. We demonstrate that our bionanowires can be used as electron-transfer mediators to build a bioelectrode for the electrocatalytic oxygen reduction by laccase. This approach opens opportunities for the engineering of protein-only electron mediators (with tunable redox potentials and optimized interactions with enzymes) and applications in the field of protein-only bioelectrodes.
Topics: Catalysis; Electrochemical Techniques; Electrodes; Electron Transport; Laccase; Metalloproteins; Methanococcus; Microscopy, Atomic Force; Nanowires; Oxidation-Reduction; Prions; Rubredoxins
PubMed: 28282052
DOI: 10.1038/nchem.2616 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2023De novo metalloprotein design involves the construction of proteins guided by specific repeat patterns of polar and apolar residues, which, upon self-assembly, provide a...
De novo metalloprotein design involves the construction of proteins guided by specific repeat patterns of polar and apolar residues, which, upon self-assembly, provide a suitable environment to bind metals and produce artificial metalloenzymes. While a wide range of functionalities have been realized in de novo designed metalloproteins, the functional repertoire of such constructs towards alternative energy-relevant catalysis is currently limited. Here we show the application of de novo approach to design a functional H evolving protein. The design involved the assembly of an amphiphilic peptide featuring cysteines at tandem a/d sites of each helix. Intriguingly, upon Ni addition, the oligomers shift from a major trimeric assembly to a mix of dimers and trimers. The metalloprotein produced H photocatalytically with a bell-shape pH dependence, having a maximum activity at pH 5.5. Transient absorption spectroscopy is used to determine the timescales of electron transfer as a function of pH. Selective outer sphere mutations are made to probe how the local environment tunes activity. A preferential enhancement of activity is observed via steric modulation above the Ni site, towards the N-termini, compared to below the Ni site towards the C-termini.
Topics: Metalloproteins; Hydrogen; Metals; Cysteine; Peptides
PubMed: 36440875
DOI: 10.1002/chem.202202902 -
Trends in Biotechnology Apr 2014Metalloproteins utilize metal cofactors to catalyze essential reactions in all organisms. They carry out thermodynamically challenging substrate conversions such as the...
Metalloproteins utilize metal cofactors to catalyze essential reactions in all organisms. They carry out thermodynamically challenging substrate conversions such as the oxidation of water or hydrocarbons, the reduction of nitrogen to ammonium, and generation of molecular hydrogen. Besides their fundamental role in nature, metalloenzymes have promising biotechnological applications that aim to generate high-value chemicals, drugs, nutrients, biofuels, or electricity. Recent reports that a chemically synthesized compound is able to reconstitute [2Fe]-hydrogenases, harboring an especially elaborate and highly efficient metal cofactor, promise to pave the way for gaining much deeper insight into the function of even complex metal enzymes. What is more, synthetic biology approaches such as the chemical synthesis of artificial hydrogenases seem to be in reach.
Topics: Biocatalysis; Biomimetic Materials; Biotechnology; Coenzymes; Metalloproteins; Models, Molecular
PubMed: 24630475
DOI: 10.1016/j.tibtech.2014.02.004 -
Metallomics : Integrated Biometal... Mar 2017With metalloproteins garnering increased interest as therapeutic targets, designing target-specific metalloprotein inhibitors (MPi) is of substantial importance....
With metalloproteins garnering increased interest as therapeutic targets, designing target-specific metalloprotein inhibitors (MPi) is of substantial importance. However, in many respects, the development and evaluation of MPi lags behind that of conventional small molecule therapeutics. Core concerns around MPi, such as target selectivity and potential disruption of metal ion homeostasis linger. Herein, we used a suite of analytical methods, including energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectroscopy (ICP-OES), and synchrotron X-ray fluorescence microscopy (SXRF) to investigate the effect of several MPi on cellular metal ion distribution and homeostasis. The results reveal that at therapeutically relevant concentrations, the tested MPi have no significant effects on cellular metal ion content or distribution. In addition, the affinity of the metal-binding pharmacophore (MBP) utilized by the MPi does not have a substantial influence on the effect of the MPi on cellular metal distribution. These studies provide an important, original data set indicating that metal ion homeostasis is not notably perturbed by MPi, which should encourage the development of and aid in designing new MPi, guide MBP selection, and clarify the effect of MPi on the 'metallome'.
Topics: Animals; Cell Survival; Fluorescence; Metalloproteins; Metals; Mice; NIH 3T3 Cells; Protease Inhibitors; Spectrometry, X-Ray Emission; Synchrotrons
PubMed: 28168254
DOI: 10.1039/c6mt00267f