Discovering structural motifs using a structural alphabet: Application to magnesium-binding sites

BACKGROUND: For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg(2+), one of the most versatile metal cofactors in cellular biochemistry. Even when Mg(2+)-proteins share insufficient sequence homology to identify Mg(2+)-specific sequence motifs, they may still share similarity in the Mg(2+)-binding site structure. However, no structural motifs characteristic of Mg(2+)-binding sites have been reported. Thus, our aims are (i) to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (ii) to apply it to Mg(2+)-proteins sharing <30% sequence identity. Our motif discovery method employs structural alphabet encoding to convert 3D structures to the corresponding 1D structural letter sequences, where the Mg(2+)-structural motifs are identified as recurring structural patterns. RESULTS: The structural alphabet-based motif discovery method has revealed the structural preference of Mg(2+)-binding sites for certain local/secondary structures: compared to all residues in the Mg(2+)-proteins, both first and second-shell Mg(2+)-ligands prefer loops to helices. Even when the Mg(2+)-proteins share no significant sequence homology, some of them share a similar Mg(2+)-binding site structure: 4 Mg(2+)-structural motifs, comprising 21% of the binding sites, were found. In particular, one of the Mg(2+)-structural motifs found maps to a specific functional group, namely, hydrolases. Furthermore, 2 of the motifs were not found in non metalloproteins or in Ca(2+)-binding proteins. The structural motifs discovered thus capture some essential biochemical and/or evolutionary properties, and hence may be useful for discovering proteins where Mg(2+ )plays an important biological role. CONCLUSION: The structural motif discovery method presented herein is general and can be applied to any set of proteins with known 3D structures. This new method is timely considering the increasing number of structures for proteins with unknown function that are being solved from structural genomics incentives. For such proteins, which share no significant sequence homology to proteins of known function, the presence of a structural motif that maps to a specific protein function in the structure would suggest likely active/binding sites and a particular biological function

Bond Properties and Molecular Conformation from Vibrational Intensity Analysis

Experimental vibrational intensities in infrared spectra can be transformed into quantities characterizing bond properties fol- lowing the formalism of the bond polar parameters model. The theory is briefly presented. An optimized set of bond polar parameters for hydrocarbons is obtained following constraints derived from experimental spectral data and ab initio MO calculations. The set of intensity parameters together with transferable force constants is used in predicting the infrared spectra of individual conformers and equilibrium conformer mixtures of n-butane-do, n-pentane-d, n-pentane-djj and n-hexane-d, The influence of rotational isomerism on infrared intensities in these systems is discussed

Discovering structural motifs using a structural alphabet: Application to magnesium-binding sites

[[abstract]]Background: For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg2+, one of the most versatile metal cofactors in cellular biochemistry. Even when Mg2+-proteins share insufficient sequence homology to identify Mg2+-specific sequence motifs, they may still share similarity in the Mg2+-binding site structure. However, no structural motifs characteristic of Mg2+-binding sites have been reported. Thus, our aims are (\i) to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (\ii) to apply it to Mg2+-proteins sharing < 30% sequence identity. Our motif discovery method employs structural alphabet encoding to convert 3D structures to the corresponding 1D structural letter sequences, where the Mg2+-structural motifs are identified as recurring structural patterns.[[fileno]]2020129010036[[fileno]]2010309010036[[department]]化學

Relationship Between Atomic Polar Tensors and Bond Polar Parameters Formulations of Infrared Intensities

The mathematical and physical aspects of the relationship between the atomic polar tensors and bond polar parameters formulations of vibrational intensities in infrared spectra are discussed. The theoretical considerations are illustrated with parallel applications of the two approaches in analysing experimental intensity data for ethane, methyl chloride and H2O

Promiscuity and preferences of metallothioneins: the cell rules

Metalloproteins are essential for many cellular functions, but it has not been clear how they distinguish between the different metals to bind the correct ones. A report in BMC Biology finds that preferences of two metallothionein isoforms for two different cations are due to inherent properties of these usually less discriminating proteins. Here these observations are discussed in the context of the cellular mechanisms that regulate metal binding to proteins

Investigation of Atomic Level Patterns in Protein—Small Ligand Interactions

BACKGROUND: Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes. METHODOLOGY AND PRINCIPAL FINDINGS: We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites. CONCLUSIONS AND SIGNIFICANCE: We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds

Fungus-Mediated Green Synthesis of Silver Nanoparticles Using Aspergillus terreus

The biosynthesis of nanoparticles has received increasing attention due to the growing need to develop safe, cost-effective and environmentally friendly technologies for nano-materials synthesis. In this report, silver nanoparticles (AgNPs) were synthesized using a reduction of aqueous Ag+ ion with the culture supernatants of Aspergillus terreus. The reaction occurred at ambient temperature and in a few hours. The bioreduction of AgNPs was monitored by ultraviolet-visible spectroscopy, and the AgNPs obtained were characterized by transmission electron microscopy and X-ray diffraction. The synthesized AgNPs were polydispersed spherical particles ranging in size from 1 to 20 nm and stabilized in the solution. Reduced nicotinamide adenine dinucleotide (NADH) was found to be an important reducing agent for the biosynthesis, and the formation of AgNPs might be an enzyme-mediated extracellular reaction process. Furthermore, the antimicrobial potential of AgNPs was systematically evaluated. The synthesized AgNPs could efficiently inhibit various pathogenic organisms, including bacteria and fungi. The current research opens a new avenue for the green synthesis of nano-materials

Minimal Functional Sites Allow a Classification of Zinc Sites in Proteins

Zinc is indispensable to all forms of life as it is an essential component of many different proteins involved in a wide range of biological processes. Not differently from other metals, zinc in proteins can play different roles that depend on the features of the metal-binding site. In this work, we describe zinc sites in proteins with known structure by means of three-dimensional templates that can be automatically extracted from PDB files and consist of the protein structure around the metal, including the zinc ligands and the residues in close spatial proximity to the ligands. This definition is devised to intrinsically capture the features of the local protein environment that can affect metal function, and corresponds to what we call a minimal functional site (MFS). We used MFSs to classify all zinc sites whose structures are available in the PDB and combined this classification with functional annotation as available in the literature. We classified 77% of zinc sites into ten clusters, each grouping zinc sites with structures that are highly similar, and an additional 16% into seven pseudo-clusters, each grouping zinc sites with structures that are only broadly similar. Sites where zinc plays a structural role are predominant in eight clusters and in two pseudo-clusters, while sites where zinc plays a catalytic role are predominant in two clusters and in five pseudo-clusters. We also analyzed the amino acid composition of the coordination sphere of zinc as a function of its role in the protein, highlighting trends and exceptions. In a period when the number of known zinc proteins is expected to grow further with the increasing awareness of the cellular mechanisms of zinc homeostasis, this classification represents a valuable basis for structure-function studies of zinc proteins, with broad applications in biochemistry, molecular pharmacology and de novo protein design