Tyrosine Ligand Research Articles

Identification, isoform classification, ligand binding, and database construction of the protein-tyrosine sulfotransferase family in metazoans

Protein tyrosine sulfonation (PTS) influences various crucial physiological and pathological processes in animals. Protein-tyrosine sulfotransferase (TPST) serves as a pivotal enzyme in this process. Research on TPST is still in its early stages, and current identification methods have not yet effectively differentiated TPST from other type II sulfotransferases. Furthermore, this study has revealed that TPST in animals is highly conserved and exhibits significant differences when compared to other sulfotransferases and TPSTs in non-animal species. However, precise and efficient methods for identifying TPST, conducting subfamily classification, performing functional and sequence analyses, and accessing corresponding databases and analytical platforms for the entire TPST family of metazoan species are lacking. These findings provide a foundation for more in-depth research on TPST in animals and are crucial for advancing the understanding of PTS and its broader impacts.In this study, a Hidden Markov Model (TPST-HMM) was formulated based on the conserved motifs binding to the substrate PAPS and the ligand tyrosine in metazoan TPSTs. TPST-HMM successfully identified more than 91.8 % of metazoan TPSTs in UniProt (e-value < 1e-5). When the threshold was adjusted to 1e-20, the identification rate of TPST was 83.9 % in metazoans and approximately 0 % in other species (fungi, bacteria, etc.). Subsequently, 5638 TPSTs were identified from 1311 metazoan genomes, and these TPSTs were classified into three subfamilies. The classification of the TPST1 and TPST2 subtypes, which were initially annotated in mammals, was extended across vertebrates. Additionally, a novel subtype, TPST3, belonging to a distinct subfamily, was discovered in invertebrates. We proposed a molecular docking prediction method for TPST and tyrosine ligands based on the observation that TPST-tyrosine binding recognition and binding in metazoans were primarily driven by electrostatic interactions.Finally, a database website for animal TPST sequences was established (http://sz.bjfskj.com/). The website included an online tool for identifying TPST protein sequences, enabling annotation and visualization of functional motifs and active amino acids. Its design aimed to assist users in studying TPST in animals.

Preparation, Characterization and Antibacterial Activities of Metal complexes with Tyrosine Ligands.

Preparation, Characterization and Antibacterial Activities of Metal complexes with Tyrosine Ligands.

Structural and functional insights into iron acquisition from lactoferrin and transferrin in Gram-negative bacterial pathogens

Iron is an essential element for various lifeforms but is largely insoluble due to the oxygenation of Earth’s atmosphere and oceans during the Proterozoic era. Metazoans evolved iron transport glycoproteins, like transferrin (Tf) and lactoferrin (Lf), to keep iron in a non-toxic, usable form, while maintaining a low free iron concentration in the body that is unable to sustain bacterial growth. To survive on the mucosal surfaces of the human respiratory tract where it exclusively resides, the Gram-negative bacterial pathogen Moraxella catarrhalis utilizes surface receptors for acquiring iron directly from human Tf and Lf. The receptors are comprised of a surface lipoprotein to capture iron-loaded Tf or Lf and deliver it to a TonB-dependent transporter (TBDT) for removal of iron and transport across the outer membrane. The subsequent transport of iron into the cell is normally mediated by a periplasmic iron-binding protein and inner membrane transport complex, which has yet to be determined for Moraxella catarrhalis. We identified two potential periplasm to cytoplasm transport systems and performed structural and functional studies with the periplasmic binding proteins (FbpA and AfeA) to evaluate their role. Growth studies with strains deleted in the fbpA or afeA gene demonstrated that FbpA, but not AfeA, was required for growth on human Tf or Lf. The crystal structure of FbpA with bound iron in the open conformation was obtained, identifying three tyrosine ligands that were required for growth on Tf or Lf. Computational modeling of the YfeA homologue, AfeA, revealed conserved residues involved in metal binding.

Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro, the largest amount of tumor site accumulation and the best antitumor effect in vivo, compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.

Supramolecular Macrostructures in the Mechanisms of Catalysis with Nickel or Iron Heteroligand Complexes

Background: The AFM-techniques have been used for the research of the role of intermolecular H-bonds and stable supramolecular nanostructures, based on effective catalysts of oxidation processes, which are also models of Ni(Fe)ARD Dioxygenases, in mechanisms of catalysis. Methods and Results: The role of Histidine and Tyrosine ligands in the mechanisms of catalysis by FeARD on model systems is discussed based on AFM and UV-Spectroscopy data. Conclusion: We first offer the new approach – method of atomic force microscopy (AFM) – to study the possibility of the formation of supramolecular nanostructures, and also for assessing of role the intermolecular hydrogen bonds (and the other intermolecular non-covalent interactions) in mechanisms of homogeneous and enzymatic catalysis with nickel and iron complexes.

Active-site maturation and activity of the copper-radical oxidase GlxA are governed by a tryptophan residue.

GlxA from Streptomyces lividans is a mononuclear copper-radical oxidase and a member of the auxiliary activity family 5 (AA5). Its domain organisation and low sequence homology make it a distinct member of the AA5 family in which the fungal galactose 6-oxidase (Gox) is the best characterised. GlxA is a key cuproenzyme in the copper-dependent morphological development of S. lividans with a function that is linked to the processing of an extracytoplasmic glycan. The catalytic sites in GlxA and Gox contain two distinct one-electron acceptors comprising the copper ion and a 3'-(S-cysteinyl) tyrosine. The latter is formed post-translationally through a covalent bond between a cysteine and a copper-co-ordinating tyrosine ligand and houses a radical. In GlxA and Gox, a second co-ordination sphere tryptophan residue (Trp288 in GlxA) is present, but the orientation of the indole ring differs between the two enzymes, creating a marked difference in the π-π stacking interaction of the benzyl ring with the 3'-(S-cysteinyl) tyrosine. Differences in the spectroscopic and enzymatic activity have been reported between GlxA and Gox with the indole orientation suggested as a reason. Here, we report a series of in vivo and in vitro studies using the W288F and W288A variants of GlxA to assess the role of Trp288 on the morphology, maturation, spectroscopic and enzymatic properties. Our findings point towards a salient role for Trp288 in the kinetics of copper loading and maturation of GlxA, with its presence essential for stabilising the metalloradical site required for coupling catalytic activity and morphological development.

Characterization of the second conserved domain in the heme uptake protein HtaA from Corynebacterium diphtheriae

HtaA is a heme-binding protein that is part of the heme uptake system in Corynebacterium diphtheriae. HtaA contains two conserved regions (CR1 and CR2). It has been previously reported that both domains can bind heme; the CR2 domain binds hemoglobin more strongly than the CR1 domain. In this study, we report the biophysical characteristics of HtaA-CR2. UV–visible spectroscopy and resonance Raman experiments are consistent with this domain containing a single heme that is bound to the protein through an axial tyrosine ligand. Mutants of conserved tyrosine and histidine residues (Y361, H412, and Y490) have been studied. These mutants are isolated with very little heme (≤5%) in comparison to the wild-type protein (~20%). Reconstitution after removal of the heme with butanone gave an alternative form of the protein. The HtaA-CR2 fold is very stable; it was necessary to perform thermal denaturation experiments in the presence of guanidinium hydrochloride. HtaA-CR2 unfolds extremely slowly; even in 6.8M GdnHCl at 37°C, the half-life was 5h. In contrast, the apo forms of WT HtaA-CR2 and the aforementioned mutants unfolded at much lower concentrations of GdnHCl, indicating the role of heme in stabilizing the structure and implying that heme transfer is effected only to a partner protein in vivo.

Corynebacterium diphtheriae HmuT: dissecting the roles of conserved residues in heme pocket stabilization.

The heme-binding protein HmuT is part of the Corynebacterium diphtheriae heme uptake pathway and is responsible for the delivery of heme to the HmuUV ABC transporter. HmuT binds heme with a conserved His/Tyr heme axial ligation motif. Sequence alignment revealed additional conserved residues of potential importance for heme binding: R237, Y272 and M292. In this study, site-directed mutations at these three positions provided insight into the nature of axial heme binding to the protein and its effect on the thermal stability of the heme-loaded protein fold. UV-visible absorbance, resonance Raman (rR) and thermal unfolding experiments, along with collision-induced dissociation electrospray ionization mass spectrometry, were used to probe the contributions of each mutated residue to the stability of ϖ HmuT. Thermal unfolding and rR experiments revealed that R237 and M292 are important residues for heme binding. Arginine 237 is a hydrogen-bond donor to the phenol side chain of Y235, which serves as an axial heme ligand. Methionine 292 serves a supporting structural role, favoring the R237 hydrogen-bond donation, which elicits a, heretofore, unobserved modulating influence on π donation by the axial tyrosine ligand in the heme carbonyl complex, HmuT-CO.

A Translational Biomedical Approach to Structural Arrangement of Amino Acids Complexes: A Combined Theoretical and Computational Study

In this short communication, respectively bonding among Boron (B3+), Aluminum (Al3+), Gallium (Ga3+), Indium (In3+) and Thallium (Tl3+) cations and Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine, Glutamic Acid, Glutamine, Glycine, Proline, Selenocysteine, Serine, Tyrosine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan and Valine ligands and also structural arrangement of the present compounds were studied, theoretically and computationally

Spectroscopic and Mutagenesis Studies of Human PGRMC1

Progesterone receptor membrane component 1 (PGRMC1) is a 25 kDa protein with an N-terminal transmembrane domain and a putative C-terminal cytochrome b5 domain. Heme-binding activity of PGRMC1 has been shown in various homologues of PGRMC1. Although the general definition of PGRMC1 is as a progesterone receptor, progesterone-binding activity has not been directly demonstrated in any of the purified PGRMC1 proteins fully loaded with heme. Here, we show that the human homologue of PGRMC1 (hPGRMC1) binds heme in a five-coordinate (5C) high-spin (HS) configuration, with an axial tyrosinate ligand, likely Y95. The negatively charged tyrosinate ligand leads to a relatively low redox potential of approximately -331 mV. The Y95C or Y95F mutation dramatically reduces the ability of the protein to bind heme, supporting the assignment of the axial heme ligand to Y95. On the other hand, the Y95H mutation retains ∼90% of the heme-binding activity. The heme in Y95H is also 5CHS, but it has a hydroxide axial ligand, conceivably stabilized by the engineered-in H95 via an H-bond; CO binding to the distal ligand-binding site leads to an exchange of the axial ligand to a histidine, possibly H95. We show that progesterone binds to hPGRMC1 and introduces spectral changes that manifest conformational changes to the heme. Our data offer the first direct evidence supporting progesterone-binding activity of PGRMC1.

Allostery mediates ligand binding to WWOX tumor suppressor via a conformational switch.

While being devoid of the ability to recognize ligands itself, the WW2 domain is believed to aid ligand binding to the WW1 domain in the context of a WW1-WW2 tandem module of WW domain-containing oxidoreductase (WWOX) tumor suppressor. In an effort to test the generality of this hypothesis, we have undertaken here a detailed biophysical analysis of the binding of WW domains of WWOX alone and in the context of the WW1-WW2 tandem module to an array of putative proline-proline-x-tyrosine (PPXY) ligands. Our data show that while the WW1 domain of WWOX binds to all ligands in a physiologically relevant manner, the WW2 domain does not. Moreover, ligand binding to the WW1 domain in the context of the WW1-WW2 tandem module is two-to-three-fold stronger than when treated alone. We also provide evidence that the WW domains within the WW1-WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. Of particular note is the observation that the physical association of the WW2 domain with WW1 blocks access to ligands. Consequently, ligand binding to the WW1 domain not only results in the displacement of the WW2 lid but also disrupts the physical association of WW domains in the liganded conformation. Taken together, our study underscores a key role of allosteric communication in the ability of the WW2 orphan domain to chaperone physiological action of the WW1 domain within the context of the WW1-WW2 tandem module of WWOX.

Spectroscopic evidence for a 5-coordinate oxygenic ligated high spin ferric heme moiety in the Neisseria meningitidis hemoglobin binding receptor

BackgroundFor many pathogenic microorganisms, iron acquisition represents a significant stress during the colonization of a mammalian host. Heme is the single most abundant source of soluble iron in this environment. While the importance of iron assimilation for nearly all organisms is clear, the mechanisms by which heme is acquired and utilized by many bacterial pathogens, even those most commonly found at sites of infection, remain poorly understood. MethodsAn alternative protocol for the production and purification of the outer membrane hemoglobin receptor (HmbR) from the pathogen Neisseria meningitidis has facilitated a biophysical characterization of this outer membrane transporter by electronic absorption, circular dichroism, electron paramagnetic resonance, and resonance Raman techniques. ResultsHmbR co-purifies with 5-coordinate high spin ferric heme bound. The heme binding site accommodates exogenous imidazole as a sixth ligand, which results in a 6-coordinate, low-spin ferric species. Both the 5- and 6-coordinate complexes are reduced by sodium hydrosulfite. Four HmbR variants with a modest decrease in binding efficiency for heme have been identified (H87C, H280A, Y282A, and Y456C). These findings are consistent with an emerging paradigm wherein the ferric iron center of bound heme is coordinated by a tyrosine ligand. ConclusionIn summary, this study provides the first spectroscopic characterization for any heme or iron transporter in Neisseria meningitidis, and suggests a coordination environment heretofore unobserved in a TonB-dependent hemin transporter. General SignificanceA detailed understanding of the nutrient acquisition pathways in common pathogens such as N. meningitidis provides a foundation for new antimicrobial strategies.

Bio-inspired Janus gold nanoclusters with lipid and amino acid functional capping ligands: micro-voltammetry and in situ electron transfer in a biogenic environment

This investigation reports the design and synthesis of bio-inspired interfacial Janus gold quantum clusters with DPPC lipid and amino acid tyrosine ligand functionalities. The lipid, anchored through steric and charge stabilization, nanoengineered the size and spatial requirements of the 2D Janus cluster array. In situ quantum charging and electron transfer in this biogenic environment revealed the role of tyrosine towards enhanced electron transfer across the Janus cluster and provided a direct clue in understanding nanoparticle-mediated interactions in a microenvironment. This work is the first report of quantized electron transfer dynamics in a Janus cluster, and it clearly depicts the role of tyrosine ligand and inter-cluster coupling during the single-electron charging of the Janus clusters, which may be extended towards understanding electron transfer at alveolar interfaces.

μ3-Methoxido-κ3O:O:O-tris(μ-L-p-tyrosinato-κ3N,O:O)tris(L-p-tyrosinato-κ2N,O)trinickel(II,III) methanol tetrasolvate

A trinuclear nickel complex, [Ni3(C9H10NO3)6(CH3O)]·4CH4O, was synthesized and characterized as a neutral cluster containing the incomplete cubane {Ni3(μ1-O)(μ2-O)2(μ3-O)} core of 2M3–1 topology. The three nickel cations show similar octa­hedral coordination, {Ni(μ1-O)(μ2-O)2(μ3-O)(μ1-N)2}; the positive charge is balanced by six tyrosinate ligands and one methoxide ion. The mean oxidation state of each NiII ion is therefore +2.33. The common coordination modes, chelating (via the amino N and the carboxyl­ate O atoms) and bridging (via the carboxyl­ate O atom), are exhibited by the tyrosinates. Three inter­ligand (intra­cluster) N—H⋯O hydrogen-bonding inter­actions stabilize the incomplete cubane-type moiety. Additional N—H⋯O, O—H⋯O and C—H⋯O inter­actions are formed between clusters, and between the clusters and methanol mol­ecules to regulate the spatial orientation of the tyrosinate and the assembly of the clusters in the crystal. The approximate equilateral triangular arrangement of the three nickel cations in the incomplete cubane-type moiety suggests the possible magnetic frustration, and the proximity of these metal cations indicates weak metallic bonds. The structure contains approximately 39% solvent-accessible volume between the clusters. This is filled with 17 mol­ecules of disordered methanol and was modelled with SQUEEZE [Spek (2009 ▶). Acta Cryst. D65, 148–155]; the reported unit-cell characteristics do not take these mol­ecules into account. The H atoms of the solvent mol­ecules have not been included in the crystal data.

Effects of the loss of the axial tyrosine ligand of the low-spin heme of MauG on its physical properties and reactivity

MauG catalyzes posttranslational modifications of methylamine dehydrogenase to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. MauG possesses a five-coordinate high-spin and a six-coordinate low-spin ferric heme, the latter with His-Tyr ligation. Replacement of this tyrosine with lysine generates a MauG variant with only high-spin ferric heme and altered spectroscopic and redox properties. Y294K MauG cannot stabilize the bis-Fe(IV) redox state required for TTQ biosynthesis but instead forms a compound I-like species on reaction with peroxide. The results clarify the role of Tyr ligation of the five-coordinate heme in determining the physical and redox properties and reactivity of MauG.

Geometric and electronic structures of the His–Fe(IV)=O and His–Fe(IV)–Tyr hemes of MauG

Biosynthesis of the tryptophan tryptophylquinone (TTQ) cofactor activates the enzyme methylamine dehydrogenase. The diheme enzyme MauG catalyzes O-atom insertion and cross-linking of two Trp residues to complete TTQ synthesis. Solution optical and Mössbauer spectroscopic studies have indicated that the reactive form of MauG during turnover is an unusual bisFe(IV) intermediate, which has been formulated as a His-ligated ferryl heme [Fe(IV)=O] (heme A), and an Fe(IV) heme with an atypical His/Tyr ligation (heme B). In this study, Fe K-edge X-ray absorption spectroscopy and extended X-ray absorption fine structure studies have been combined with density functional theory (DFT) and time-dependent DFT methods to solve the geometric and electronic structures of each heme site in the MauG bisFe(IV) redox state. The ferryl heme site (heme A) is compared with the well-characterized compound I intermediate of cytochrome c peroxidase. Heme B is unprecedented in biology, and is shown to have a six-coordinate, S = 1 environment, with a short (1.85-Å) Fe-O(Tyr) bond. Experimentally calibrated DFT calculations are used to reveal a strong covalent interaction between the Fe and the O(Tyr) ligand of heme B in the high-valence form. A large change in the Fe-O(Tyr) bond distance on going from Fe(II) (2.02 Å) to Fe(III) (1.89 Å) to Fe(IV) (1.85 Å) signifies increasing localization of spin density on the tyrosinate ligand upon sequential oxidation of heme B to Fe(IV). As such, O(Tyr) plays an active role in attaining and stabilizing the MauG bisFe(IV) redox state.

Can Uranium Be Transported by the Iron-Acquisition Pathway? Ur Uptake by Transferrin

Transferrin (T) is one of the major protein targets of uranyl (Ur) and the Ur-loaded protein (TUr(2)) interacts with receptor 1. In vitro, Ur is transferred from one of the major plasma complexes, tricarbonated Ur (Ur(CO(3))(3)(4-)) to T in four kinetically differentiated steps. The first is very fast and accompanied by HCO(3)(-) loss. It yields a first intermediate ternary complex between dicarbonated Ur and the phenolate of one of the two tyrosine ligands in the C-lobe; direct rate constant, k(1) = (7.0 ± 0.4) × 10(5) M(-1) s(-1); reverse rate constant, k(-1) = (4.7 ± 0.2) × 10(3) M(-1) s(-1); dissociation constant, K(1) = (6.7 ± 0.6) × 10(-3) and an affinity of the T for the dicarbonated Ur (Ur(CO(3))(2)(2-)) close to that of the latter to CO(3)(2-), K'(3) ~ 1 × 10(4). This first kinetic product undertakes a fast rate-limiting conformation change leading to the loss of a second HCO(3)(-): direct rate constant, k(2) = 33 ± 14 s(-1). This second ternary complex undergoes two very slow conformation changes (1 and 5 h), at the end of which both C- and N-lobes become loaded with Ur. When unexposed to uranium, the Ur concentrations in the bloodstream are much too low to favor receptor-mediated transport. However, in the case of exposure, these concentrations can grow considerably. This, added to the fast Ur complex formation with the C-lobe and the fast interaction of the Ur-loaded T with the receptor, can allow a possible internalization by the iron-acquisition pathway.

The mechanism of the reaction of intradiol dioxygenase with hydroperoxy probe: A DFT study

The mechanism for the reaction between an intradiol dioxygenase and a hydroperoxy probe was modeled with the DFT method – B3LYP. Five models of the iron cofactor – probe complexes differing in the total charge and the number of ligands bound to iron were considered. The most important conclusion from the study described in this contribution is that the critical O–O bond cleavage, leading to the alkoxyl radical intermediate, most likely does not yield the reactive oxoferryl species. Instead, in the preferred reaction channel the peroxo group is protonated and the O–O cleavage leads to the ferrous complex with one of the tyrosine ligands oxidized to the tyrosinate radical. The factors affecting the product specificity are also discussed in the paper.

A density functional investigation of hydrogen peroxide activation by high-valent heme centers: implications for the catalase catalytic cycle

Catalases employ a tyrosinate-ligated ferric heme in order to catalyze the dismutation of hydrogen peroxide to O2 and water. In the first half of the catalytic cycle, H2O2 oxidizes Fe(III) to the formally Fe(V) state commonly referred to as Compound I. The second half of the cycle entails oxidation of a second hydrogen peroxide molecule by Compound I to dioxygen. The present study employs density functional (DFT) calculations to examine the nature of this second step of the catalatic reaction. In order to account for the unusual choice of tyrosinate as an axial ligand in catalases, oxidation of hydrogen peroxide by an imidazole-ligated Compound I is also examined, bearing in mind that imidazole-ligated hemoproteins such as myoglobin or horseradish peroxidase tend to display little, if any, catalatic activity. Furthermore, in order to gauge the importance of the cation radical of Compound I in peroxide activation, the performance of Compound II (the one-electron reduced version of Compound I, formally Fe(IV) ), is also examined. It is found that hydrogen peroxide oxidation occurs in a quasi-concerted manner, with two hydrogen-atom transfer reactions, and that the tyrosinate ligand is in no way required at this stage. We propose that the role of the tyrosinate is purely thermodynamic, in avoiding accumulation of the much less peroxide-reactive ferrous form in vivo – all in line with the predominantly thermodynamic role of the cysteinate ligands in enzymes such as cytochromes P450.

Surface modification with multiphilic ligands at detectable well defined active positions of nano-object of giant wheel shaped molybdenum blue showing third-order nonlinear optical properties

The reaction of an aqueous solution of sodium molybdate with l-tyrosine in the presence of reducing agent results in the formation of a new compound of the formula of Na 8Co 3[Mo VI 126 Mo V 28O 462H 14(H 2O) 46(HOC 6H 4CH 2CH( NH 3 + )COO −) 12]·ca. 200H 2O. The compound contains nanosized ring-shaped clusters with tyrosine ligands possessing different types of functional groups (one –CO 2, one – NH 3 + and one –ArOH) coordinated through the carboxylate groups at the active sites of the inner cavity. Importantly, the result demonstrates that not only active sites/areas of the cluster surface under a specified condition can be directly monitored and detected but also novel type surfaces within the cavity of a nano-structured ring-shaped cluster can be generated simultaneously. The nonlinear optical properties of the new cluster are studied using the well-known Z-scan technique at a wavelength of 532 nm with laser pulse duration of 18 ps. The results show that the new cluster exhibits interesting self-focusing nonlinear optical response with the real and imaginary parts of the third-order nonlinear optical susceptibility χ (3) being 1.069 × 10 −13(esu) and 2.529 × 10 −15(esu), respectively, which may find application in material science.