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Molecules (Basel, Switzerland) Jul 2020Trace metals are inorganic elements that are required for all organisms in very low quantities. They serve as cofactors and activators of metalloproteins involved in a... (Review)
Review
Trace metals are inorganic elements that are required for all organisms in very low quantities. They serve as cofactors and activators of metalloproteins involved in a variety of key cellular processes. While substantial effort has been made in experimental characterization of metalloproteins and their functions, the application of bioinformatics in the research of metalloproteins and metalloproteomes is still limited. In the last few years, computational prediction and comparative genomics of metalloprotein genes have arisen, which provide significant insights into their distribution, function, and evolution in nature. This review aims to offer an overview of recent advances in bioinformatic analysis of metalloproteins, mainly focusing on metalloprotein prediction and the use of different metals across the tree of life. We describe current computational approaches for the identification of metalloprotein genes and metal-binding sites/patterns in proteins, and then introduce a set of related databases. Furthermore, we discuss the latest research progress in comparative genomics of several important metals in both prokaryotes and eukaryotes, which demonstrates divergent and dynamic evolutionary patterns of different metalloprotein families and metalloproteomes. Overall, bioinformatic studies of metalloproteins provide a foundation for systematic understanding of trace metal utilization in all three domains of life.
Topics: Animals; Binding Sites; Computational Biology; Eukaryota; Genomics; Humans; Metalloproteins; Prokaryotic Cells; Proteome; Trace Elements
PubMed: 32722260
DOI: 10.3390/molecules25153366 -
Chembiochem : a European Journal of... Jun 2020The nitrogenase superfamily comprises homologous enzyme systems that carry out fundamentally important processes, including the reduction of N and CO, and the...
The nitrogenase superfamily comprises homologous enzyme systems that carry out fundamentally important processes, including the reduction of N and CO, and the biosynthesis of bacteriochlorophyll and coenzyme F430. This special issue provides a cross-disciplinary overview of the ongoing research in this highly diverse and unique research area of metalloprotein biochemistry.
Topics: Metalloproteins; Nitrogenase; Oxidation-Reduction
PubMed: 32426925
DOI: 10.1002/cbic.202000279 -
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 -
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 -
Methods in Molecular Biology (Clifton,... 2019An overview of modern methods used in the preparation and characterization of molybdenum-containing enzymes is presented, with an emphasis on those methods that have...
An overview of modern methods used in the preparation and characterization of molybdenum-containing enzymes is presented, with an emphasis on those methods that have been developed over the past decade to address specific difficulties frequently encountered in studies of these enzymes.
Topics: Anaerobiosis; Metalloproteins; Molybdenum; Oxygen
PubMed: 30317474
DOI: 10.1007/978-1-4939-8864-8_4 -
Biochimica Et Biophysica Acta.... Jan 2021The molybdenum cofactor (Moco) represents an ancient metal‑sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual... (Review)
Review
The molybdenum cofactor (Moco) represents an ancient metal‑sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual and global scale. Given the diversity of biological processes dependent on Moco and their evolutionary age, Moco is traced back to the last universal common ancestor (LUCA), while Moco biosynthetic genes underwent significant changes through evolution and acquired additional functions. In this review, focused on eukaryotic Moco biology, we elucidate the benefits of gene fusions on Moco biosynthesis and beyond. While originally the gene fusions were driven by biosynthetic advantages such as coordinated expression of functionally related proteins and product/substrate channeling, they also served as origin for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and loss of the according gene products result in severe disorders, both related to Moco biosynthesis and secondary enzyme functions.
Topics: Coenzymes; Eukaryota; Gene Fusion; Humans; Metalloproteins; Molybdenum; Molybdenum Cofactors; Pteridines; Substrate Specificity
PubMed: 33017596
DOI: 10.1016/j.bbamcr.2020.118883 -
The Journal of Biological Chemistry Mar 2018Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has... (Review)
Review
Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has toxic effects in cells, which is why eukaryotes and prokaryotes have evolved mechanisms for safe copper handling. A new family of bacterial proteins uses a Cys-rich four-helix bundle to safely store large quantities of Cu(I). The work leading to the discovery of these proteins, their properties and physiological functions, and how their presence potentially impacts the current views of bacterial copper handling and use are discussed in this review.
Topics: Bacteria; Bacterial Proteins; Copper; Metalloproteins
PubMed: 29414794
DOI: 10.1074/jbc.TM117.000180 -
Molecules (Basel, Switzerland) Feb 2022Metalloproteins are a family of proteins characterized by metal ion binding, whereby the presence of these ions confers key catalytic and ligand-binding properties. Due... (Review)
Review
Metalloproteins are a family of proteins characterized by metal ion binding, whereby the presence of these ions confers key catalytic and ligand-binding properties. Due to their ubiquity among biological systems, researchers have made immense efforts to predict the structural and functional roles of metalloproteins. Ultimately, having a comprehensive understanding of metalloproteins will lead to tangible applications, such as designing potent inhibitors in drug discovery. Recently, there has been an acceleration in the number of studies applying machine learning to predict metalloprotein properties, primarily driven by the advent of more sophisticated machine learning algorithms. This review covers how machine learning tools have consolidated and expanded our comprehension of various aspects of metalloproteins (structure, function, stability, ligand-binding interactions, and inhibitors). Future avenues of exploration are also discussed.
Topics: Amino Acid Sequence; Binding Sites; Drug Design; Machine Learning; Metalloproteins; Models, Molecular; Protein Binding; Protein Stability; Proteolysis; Structure-Activity Relationship
PubMed: 35209064
DOI: 10.3390/molecules27041277 -
Frontiers in Cellular and Infection... 2022Transition metals are essential for metalloprotein function among all domains of life. Humans utilize nutritional immunity to limit bacterial infections, employing... (Review)
Review
Transition metals are essential for metalloprotein function among all domains of life. Humans utilize nutritional immunity to limit bacterial infections, employing metalloproteins such as hemoglobin, transferrin, and lactoferrin across a variety of physiological niches to sequester iron from invading bacteria. Consequently, some bacteria have evolved mechanisms to pirate the sequestered metals and thrive in these metal-restricted environments. , the causative agent of the sexually transmitted infection gonorrhea, causes devastating disease worldwide and is an example of a bacterium capable of circumventing human nutritional immunity. production of specific outer-membrane metallotransporters, is capable of extracting iron directly from human innate immunity metalloproteins. This review focuses on the function and expression of each metalloprotein at gonococcal infection sites, as well as what is known about how the gonococcus accesses bound iron.
Topics: Gonorrhea; Hemoglobins; Humans; Iron; Lactoferrin; Metalloproteins; Neisseria gonorrhoeae
PubMed: 36189345
DOI: 10.3389/fcimb.2022.1017348 -
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