Structure Of Fc Research Articles

Benign Decay vs. Photolysis in the Photophysics and Photochemistry of 5-Bromouracil. A Computational Study

The excited state potential energy surface of 5-bromouracil has been studied with ab initio CASPT2//CASSCF calculations to rationalize the competition between the benign decay and the photolysis found experimentally. The surface is characterized by an extended region of degeneracy between S(1) and S(0). The access to this region has been studied with minimum energy path calculations from the FC structure, the seam of intersection has been mapped in detail, and the decay paths from different regions of the seam have been characterized. There are two decay paths with low barriers that are limiting cases for the actual decay dynamics. The first path involves the bromine elimination and leads to a region of near degeneracy between the ground and excited states, and the second one leads back to the reactant through a conical intersection between the two states. The conical intersection for benign decay is part of a seam that lies along the C(5)-Br stretching coordinate, and decay at the region of the seam with a stretched C(5)-Br bond leads to photolysis. Thus, the reactivity depends on the point of the seam at which decay to the ground state takes place. The low experimental photolysis quantum yield suggests that the energetically favored decay is the one that regenerates the reactant, while the low barriers computed to access the region of decay are in agreement with the measured picosecond excited state lifetime.

Experimental and quantum chemical investigation on fluorocarbonylsulfenyl benzoate, FC(O)SOC(O)C 6H 5

The novel compound fluorocarbonylsulfenyl benzoate, FC(O)SOC(O)C 6H 5, has been generated through a convenient way by gas–solid reaction between FC(O)SCl and AgOC(O)C 6H 5. The electronic structure of FC(O)SOC(O)C 6H 5 has been studied by photoelectron spectroscopy (PES), together with quantum chemical calculations. The compound prefers a gauche conformation with both C O bonds syn to the S O bond as the most stable conformation. In FC(O)SOC(O)C 6H 5, the S O bond length and the dihedral angle around S O bond for the most stable conformer are 1.687 Å and 82.2° (B3LYP/6-311++G(d,p)), respectively. The outermost electrons of FC(O)SOC(O)C 6H 5 reside in benzyl ring, and the experimental first vertical ionization energy of FC(O)SOC(O)C 6H 5 is 9.88 eV.

Complex structure of fullerene star ionomers and sodium dodecyl sulfate resolved by contrast variation with SANS and SAXS

Small angle neutron scattering and small angle X-ray scattering (SANS and SAXS) were used to resolve the complex structure formed by fullerene-based ionomers (FC 4S) and sodium dodecyl sulfate (SDS) in aqueous solution. With contrast variations provided by deuterated and protonated SDS for SANS and SAXS, the structure of FC 4S/SDS aggregates, including the complex aggregation numbers, size, and shape, was obtained.

Gas‐Phase Generation, Structure, Spectroscopy, and Quantum Chemical Calculations of Fluorocarbonylsulfur Thiocyanate, FC(O)SSCN

AbstractFluorocarbonylsulfur thiocyanate, FC(O)SSCN, was generated in the gas phase from a gas–solid reaction of FC(O)SCl on the surface of finely powdered AgSCN. The reaction products were detected and characterized in situ by photoelectron spectroscopy (PES) and photoionization mass spectrometry (PIMS). The geometrical and electronic structures of FC(O)SSCN were investigated by a combination of PES and PIMS experiments, and theoretical calculations. The title compound prefers a gauche conformation with the C=O groups syn to the S–S bond; the structure of the CSSC moiety is characterized by a dihedral angle δCSSC = 89.5° and a bond length rSS = 2.071 Å [at the B3LYP/6‐311+G(3df) level] resulting from the sulfur–sulfur lone‐pair interactions. After ionization the ground cationic‐radical form of FC(O)SSCN·+ adopts a trans‐planar structure (δCSSC = 180°) with Cs symmetry. The outermost electrons of FC(O)SSCN reside in the lone pair of the sulfur atom bonded to the C≡N group and the π‐bond between the C and N atoms, and the experimental first vertical ionization energy of FC(O)SSCN is 10.89 eV. The possible ionization and dissociation processes of FC(O)SSCN are also discussed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Structure and Stability Changes of Human IgG1 Fc as a Consequence of Methionine Oxidation

The Fc region has two highly conserved methionine residues, Met 33 (C(H)3 domain) and Met 209 (C(H)3 domain), which are important for the Fc's structure and biological function. To understand the effect of methionine oxidation on the structure and stability of the human IgG1 Fc expressed in Escherichia coli, we have characterized the fully oxidized Fc using biophysical (DSC, CD, and NMR) and bioanalytical (SEC and RP-HPLC-MS) methods. Methionine oxidation resulted in a detectable secondary and tertiary structural alteration measured by circular dichroism. This is further supported by the NMR data. The HSQC spectral changes indicate the structures of both C(H)2 and C(H)3 domains are affected by methionine oxidation. The melting temperature (Tm) of the C(H)2 domain of the human IgG1 Fc was significantly reduced upon methionine oxidation, while the melting temperature of the C(H)3 domain was only affected slightly. The change in the C(H)2 domain T m depended on the extent of oxidation of both Met 33 and Met 209. This was confirmed by DSC analysis of methionine-oxidized samples of two site specific methionine mutants. When incubated at 45 degrees C, the oxidized Fc exhibited an increased aggregation rate. In addition, the oxidized Fc displayed an increased deamidation (at pH 7.4) rate at the Asn 67 and Asn 96 sites, both located on the C(H)2 domain, while the deamidation rates of the other residues were not affected. The methionine oxidation resulted in changes in the structure and stability of the Fc, which are primarily localized to the C(H)2 domain. These changes can impact the Fc's physical and covalent stability and potentially its biological functions; therefore, it is critical to monitor and control methionine oxidation during manufacturing and storage of protein therapeutics.

Structure and function of Fc epsilon receptor II (Fc epsilon RII/CD23): a point of contact between the effector phase of allergy and B cell differentiation.

The Fc epsilon receptor II (Fc epsilon RII/CD23) has been proposed to have multiple functions as a membrane-bound or soluble molecule: a function in B cell growth and differentiation and a role in the effector phase of IgE-mediated immunity. We recently demonstrated the presence of two forms of Fc epsilon RII (Fc epsilon RIIa and Fc epsilon RIIb) whose structures differ only at their N-terminal cytoplasmic regions. The regulatory mechanisms of their expression strongly suggest that Fc epsilon RIIa and Fc epsilon RIIb function in B cells and in the effector cells of IgE-mediated immunity, respectively. To elucidate the function of soluble Fc epsilon RII/CD23 (sFc epsilon RII) the recombinant soluble molecule was produced. This recombinant receptor could competitively block the IgE binding of eosinophils, monocytes and even basophils and could inhibit the IgE-mediated function of effector cells such as monocytes. These findings suggested that sFc epsilon RII could competitively regulate the function of effector cells in IgE-mediated immunity and that the recombinant sFc epsilon RII could be applied clinically for the control of allergic reactions. The expression of Fc epsilon RII on Fc epsilon RII-negative B and T cell lines by cDNA transfection resulted in homocytic aggregation. The function of Fc epsilon RII on B cells as an adhesion molecule was also demonstrated.

Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention

Infection with dengue virus (DENV) or any other flavivirus induces cross-reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizing concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of ADE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH(2) domain in the Fc region abrogated the enhancing activity.

Agalactosylated IgG antibodies depend on cellular Fc receptors forin vivoactivity

IgG antibodies are glycoproteins containing a branched sugar moiety attached to the asparagine 297 residue in the antibody constant region (Fc). This glycan is essential for maintaining a functional Fc structure, which is a prerequisite for antibody-mediated effector functions, such as the interaction with cellular Fc receptors or the complement component C1q. Variations in the composition of the sugar moiety can dramatically influence antibody activity. Moreover, humans and mice with autoimmune disorders, such as rheumatoid arthritis, have altered IgG glycosylation patterns with increased levels of antibodies lacking terminal sialic acid and galactose residues (IgG-G0). There is great interest in understanding whether this altered glycosylation pattern influences antibody-mediated effector functions. In vitro studies have suggested that IgG-G0 antibodies gain the capacity to activate the complement pathway via mannose-binding lectin (MBL), which could contribute to antibody-mediated inflammation. We have analyzed the activity of IgG-G0 antibodies in mice with a genetic deletion of MBL (MBL-null mice) and demonstrate that IgG-G0 antibodies are unimpaired in MBL-null mice. In contrast, the activity of these antibody glycovariants is fully dependent on the presence of activating Fc receptors.

Matrix metalloproteinase-1 takes advantage of the induced fit mechanism to cleave the triple-helical type I collagen molecule.

The collagenases are members of the matrix metalloproteinase family (MMP) that degrade native triple-helical type I collagen. To understand the mechanism by which these enzymes recognize and cleave this substrate, we studied the substrate specificity of a modified form of MMP-1 (FC) in which its active site region (amino acids 212-254) had been replaced with that of MMP-9 (amino acids 395-437). Although this substitution increased the activity of the enzyme toward gelatin and the peptide substrate Mca-PLGL(Dpa)AR-NH2 by approximately 3- and approximately 11-fold, respectively, it decreased the type I collagenolytic activity of the enzyme to 0.13%. The replacement of Gly233, the only amino acid in this region of FC that is conserved in all collagenase family members, with the corresponding Glu residue in MMP-9 resulted in a substantial decrease in the type I collagenolytic activity of the enzyme without affecting its general proteolytic activities. The kinetic parameters of the FC/G233E mutant for the collagen substrate were similar to those of the chimeric enzyme. In addition, substituting Gly233 for Glu in the chimera increased the collagenolytic activity of the enzyme by 12-fold. Interestingly, replacing Glu415 in MMP-9 with Gly, its corresponding residue in FC, endowed the enzyme with type I collagenolytic activity. The catalytic activity of the MMP-9 mutant toward triple-helical type I collagen was 2-fold higher than that of the collagenase chimera. These data in conjunction with the X-ray crystal structure of FC indicate that Gly233 provides the flexibility necessary for the enzyme active site to change conformation upon substrate binding. The flexibility provided by the Gly residue is essential for type I collagenolytic activity.

Luminescent Phosphine Gold(I) Thiolates: Correlation between Crystal Structure and Photoluminescent Properties in [R3PAu{SC(OMe)NC6H4NO2-4}] (R = Et, Cy, Ph) and [(Ph2P-R-PPh2){AuSC(OMe)NC6H4NO2-4}2] (R = CH2, (CH2)2, (CH2)3, (CH2)4, Fc)

X-ray crystallography shows the gold atoms in [R3PAu{SC(OMe)=NC6H4NO2-4}] (R = Et, Cy, Ph; 1-3, respectively) and [(Ph2P-R-PPh2){AuSC(OMe)=NC6H4NO2-4}(2)] (R = CH2, (CH2)2, (CH2)3, (CH2)4, Fc; 4-8, respectively) are linearly coordinated by phosphorus and thiolate-sulfur; weak intramolecular Au...O interactions are featured in all structures. The smaller ethyl substituents in 1 allow for supramolecular association via Au...S and Au...Au interactions that are not found in 2 and 3, which contain larger phosphorus-bound Cy and Ph groups, respectively. Intramolecular Au...Au interactions are found in the dppm, dppe, dppp, and Fc structures but not in the dppp analogue, for which an anti conformation was found. The structures have been correlated with the results from photophysical study conducted in the solid state. Thus, photoexcitation of 1-7 with lambda > 350 in the solid state and in solution produces green and blue luminescence, respectively. The spectra in each medium are remarkably similar to each other, and so the emission energy and excitation maxima observed for 1-7 appear to be independent of the nature of the ancillary phosphines, as well as the presence or absence of Au...Au interactions, either intermolecularly or intramolecularly.

Trapped: A Molecular-Level Look at How Herpes Disables Its Immune Destroyer

It's not easy coming out ahead in the virus–host battle: the mechanisms living things have for seeking and destroying invaders, as elaborate as they might be, often find themselves up against equally elaborate viral mechanisms for evading them. Such is the case when it comes to humans versus herpes simplex virus type-1 (HSV-1), a highly contagious virus that is virtually impossible to get rid of once it becomes established. When our bodies detect HSV-1 inside us, they mass produce antibodies called immunoglobulin G (IgG). These Y-shaped defense molecules latch onto antigens on the surface of the virus and virus-infected cells with their two arms, disabling them and marking them for pickup by the immune-system equivalent of roving trash trucks. But HSV-1 has a cagey way of turning the tables. A protein pair that it stations on its surface (and on the surface of cells it has taken over) known as gE-gI can grab IgG by its tail (known formally as its Fc region), incapacitating it instead. Elizabeth Sprague, Pamela Bjorkman, and colleagues explored this interaction by focusing their attention on CgE, a portion of gE. Using an assay that measures how well two substances stick to each other, they showed that CgE binds Fc even in the absence of gI or other gE domains. They then used a technique that compares how crystals of CgE diffract X rays of various wavelengths to determine the three-dimensional structure of CgE. Next the researchers attempted to create a three-dimensional picture of the gE-gI/Fc complex. Using the new information about CgE's structure, low-resolution images of gE-gI/Fc crystals, and techniques that make it possible to infer complete structure from partial information, they proposed a structure for the gE-gI/Fc complex in which two CgE components of gE-gI hold Fc like two hands holding a basketball. To substantiate that surmised structure, they applied a computational approach called protein docking, using what they knew about the structure of unbound CgE and Fc to calculate what complex would be energetically most favorable. Of the five plausible models they came up with, one was remarkably similar to the structure derived through the previous process, confirming its likelihood as the correct structure. The researchers then used the newfound structural information to further explore the gE-gI/Fc interaction. They compared CgE with other proteins and a peptide of known structure that bind with the same region of Fc. They also used the structural information to explain on a molecular level the previously known inability of an Fc mutant, another human immunoglobulin, and rodent IgG to bind with gE-gI. One fascinating mystery the structures helped the researchers address is the fact that gE-gI binds well with Fc at neutral or slightly basic pH, but not in an acidic environment. The researchers showed that CgE-Fc binding is pH dependent, and attributed this trait to four histidine amino acids at the CgE/Fc interface that would likely alter the complex's chemistry in the presence of spare protons. They also speculated that the pH sensitivity was part of a viral strategy for attacking IgG in which gE-gI/IgG is drawn into the cell where the acidity causes the antibody to dissociate and eventually to be destroyed. The structural studies also shed light on previous findings regarding the effects of mutations in gE on its ability to bind IgG and on cell-to-cell spread of HSV-1. Using their knowledge of CgE and gE-gI/Fc structures, the researchers were able to identify the structural and functional implications of various mutations and to pinpoint specific regions of CgE implicated in cell-to-cell spread. Finally, the researchers used the structures to determine that gE-gI/IgG complexes likely orient upright in the cell membrane, leaving the arms of the gE-gI-bound IgG available to attach to a nearby HSV-1 antigen—a previously hypothesized state known as bipolar bridging. If bipolar bridging does indeed occur, subsequent endocytosis would then swallow up not only IgG but also any antigens involved in bridging, further hindering efforts to win the battle against this tricky viral invader.

Glycosylation in the Fc domain of IgG increases resistance to proteolytic cleavage by papain

IgG antibodies (Abs) and fragments of IgG Abs are becoming major biotherapeutics to treat an assortment of human diseases. Commonly prepared fragments of IgGs include Fc, Fab, and F(ab′)2 fragments, all of which can be made using the sulfhydryl protease papain, although prolonged digestion times and/or excessive amounts of papain typically result in further cleavage of the Fc domain into smaller fragments. During our attempts to use papain to isolate Fc fragments from different IgG monoclonal Abs, it was observed that prior removal of Fc glycans resulted in a faster rate of papain-mediated degradation of the Fc domain. Subsequent time-course experiments comparing glycosylated and deglycosylated versions of IgG antibodies showed that the majority of molecules in a deglycosylated IgG sample were converted into Fab, Fc, and smaller Fc fragments in less than one hour, whereas the original glycosylated IgG required more than two hours to convert into a comparable amount of Fab and Fc fragments. Furthermore, whereas papain digestion converted almost all of a deglycosylated Fc fragment into smaller fragments of ∼10 and ∼12 kDa within 4 h, more than 40% of a glycosylated Fc fragment remained intact even after 24 h of digestion. These results indicate that the presence of CH 2 domain glycans in either IgGs or purified Fc fragments increases resistance to papain digestion. Increased sensitivity of non-glycosylated Fc domains to papain is consistent with the Fc domains lacking a defined structure, as exemplified by their inability to bind Fcγ receptors, since misfolded proteins are often degraded by proteases because of increased accessibility of their proteolytic cleavage sites. Based on these observations it is possible to use papain sensitivity as a means of assessing proper Fc structure of IgG molecules.

A Competitive Mechanism for Staphylococcal Toxin SSL7 Inhibiting the Leukocyte IgA Receptor, FcαRI, Is Revealed by SSL7 Binding at the Cα2/Cα3 Interface of IgA

Leukocyte recruitment and effector functions like phagocytosis and respiratory burst are key elements of immunity to infection. Pathogen survival is dependent upon the ability to overwhelm, evade or inhibit the immune system. Pathogenic group A and group B streptococci are well known to produce virulence factors that block the binding of IgA to the leukocyte IgA receptor, Fc alphaRI, thereby inhibiting IgA-mediated immunity. Recently we found Staphylococcus aureus also interferes with IgA-mediated effector functions as the putative virulence factor SSL7 also binds IgA and blocks binding to Fc alphaRI. Herein we report that SSL7 and Fc alphaRI bind many of the same key residues in the Fc region of human IgA. Residues Leu-257 and Leu-258 in domain C alpha2 and residues 440-443 PLAF in C alpha3 of IgA lie at the C alpha2/C alpha3 interface and make major contributions to the binding of both the leukocyte receptor Fc alphaRI and SSL7. It is remarkable this S. aureus IgA binding factor and unrelated factors from streptococci are functionally convergent, all targeting a number of the same residues in the IgA Fc, which comprise the binding site for the leukocyte IgA receptor, Fc alphaRI.

Structure of an RNA polymerase II–RNA inhibitor complex elucidates transcription regulation by noncoding RNAs

The noncoding RNA B2 and the RNA aptamer FC bind RNA polymerase (Pol) II and inhibit messenger RNA transcription initiation, but not elongation. We report the crystal structure of FC(*), the central part of FC RNA, bound to Pol II. FC(*) RNA forms a double stem-loop structure in the Pol II active center cleft. B2 RNA may bind similarly, as it competes with FC(*) RNA for Pol II interaction. Both RNA inhibitors apparently prevent the downstream DNA duplex and the template single strand from entering the cleft after DNA melting and thus interfere with open-complex formation. Elongation is not inhibited, as nucleic acids prebound in the cleft would exclude the RNA inhibitors. The structure also indicates that A-form RNA could interact with Pol II similarly to a B-form DNA promoter, as suggested for the bacterial transcription inhibitor 6S RNA.

Anti-CD20 Monoclonal Antibody (mAb) with Enhanced Affinity for CD16 Activates NK Cells at Lower Concentrations and More Effectively Than Rituximab ®.

Growing evidence indicates the affinity of mAb for CD16 (FcgRIII) plays a central role in the ability of the mAb to mediate anti-tumor activity. Both polymorphisms in CD16 and structure of mAb Fc can impact on the affinity between CD16 and mAb. Little is known about how affinity between mAb and CD16 impacts on the ability of mAb to activate NK cells. We evaluated how CD16 polymorphisms, and mAb with modified affinity for CD16, impact on NK cell phenotype and cytokine production. MAb consisted of R, anti-CD20 with enhanced affinity for CD20 (AME-133), and AME-133 with Fc engineered to have enhanced affinity for both CD20 and CD16 (Fc-eng-133). Peripheral blood mononuclear cells were obtained from normal subjects that were homozygous for high affinity CD16 (VV at position 158), homozygous low affinity (FF at 158), and heterozygotes and were mixed with mAb and Raji lymphoma cells at an effector:target ratio of 1:1. Higher concentrations of mAb were needed to induce CD16 modulation, CD54 upregulation, and IFNg production on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with Fc-eng-133 irrespective of CD16 polymorphism.Measure of activation - % of NK cells CD54 bright: EC50 ng/ml (mean moAb concentration +/− SEM): N=4 per polymorphismRAME-133Fc-eng-133VV6.2 +/− 1.03.9 +/− 0.51.0 +/− 0.3VF11.6 +/− 1.75.7 +/− 0.61.4 +/− 0.4FF29.9 +/− 10.611.5 +/− 2.52.8 +/− 0.3p value VV vs FF<0.05<0.05<0.05p<0.01 - R vs AME-133; R vs Fc-eng-133; AME-133 vs Fc-eng-133 for each polymorphismAt saturating mAb concentrations, peak NK activation was greater for Fc engineered AME-133 when compared to R mAb for all samples studiedRatio of Fc-eng-133 to R% NK cells CD54 bright1.35 +/− 0.07IFNg production2.64 +/− 0.43These data indicate tumor cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and provide further evidence for the clinical development of such mAb with the goal of improving clinical response to mAb.

Synthesis and Characterization of (CHCH)3-Bridged Heterobimetallic Ferrocene−Ruthenium Complexes

The complex Fc(CHCH)2C⋮C-TMS (Fc = ferrocenyl) was obtained from Wittig olefination of FcCH2PPh3Br with TMS-C⋮CCHCHCHO in THF. The conjugated monometallic diene can be desilylated to give Fc(CHCH)2C⋮CH, which reacted with RuHCl(CO)(PPh3)3 to produce Fc(CHCH)3RuCl(CO)(PPh3)2. Treatment of the latter complex with PMe3, 4-phenylpyridine (PhPy), 2,6-(Ph2PCH2)2C5H3N (PMP), and KTp (Tp = hydridotris(pyrazolyl)borate) gave Fc(CHCH)3RuCl(CO)(PMe3)3, Fc(CHCH)3RuCl(CO)(PhPy)(PPh3)2, Fc(CHCH)3RuCl(CO)(PMP), and Fc(CHCH)3RuTp(CO)(PPh3), respectively. The structures of Fc(CHCH)2C⋮CH and Fc(CHCH)3RuCl(CO)(PMe3)3 have been confirmed by X-ray diffraction.

Molecular structure, spectroscopy and matrix photochemistry of fluorocarbonyl iodide, FC(O)I.

The molecular structure of FC(O)I has been determined by gas electron diffraction. High-level ab initio methods, including coupled-cluster and the new correlation-consistent basis sets for fourth row elements, have been used to calculate the structure of FC(O)I. A comprehensive vibrational spectroscopic study (both IR and Raman) complemented by high-level calculations has also been performed. Furthermore, UV, mass, and NMR spectra have been recorded for FC(O)I. The matrix photochemistry of FC(O)I has been studied with a low-pressure mercury lamp and with a high-pressure xenon lamp in combination with interference and cut-off filters. UV photolysis revealed the formation of the OC. IF and OC.FI complexes and further photolysis of these complexes at lambda>320 nm resulted in a re-formation of FC(O)I. The structural conformation of the complexes has been characterized by comparing shifts in their CO and IF vibrational modes with respect to those of the free species. The structures, vibrational properties, and stability of the complexes were analyzed with the aid of coupled-cluster ab initio calculations.

Serendipity and design in the generation of new coordination polymers: an extensive series of highly symmetrical guanidinium-templated, carbonate-based networks with the sodalite topology.

The serendipitous discovery of a 3D [Cu(CO(3))(2)(2-)](n) network with the topology of the 4(2)6(4) sodalite net in [Cu(6)(CO(3))(12)(CH(6)N(3))(8)].K(4).8H(2)O paved the way for the deliberate engineering of an extensive series of structurally related guanidinium-templated metal carbonates of composition [M(6)(CO(3))(12)(CH(6)N(3))(8)]Na(3-)[N(CH(3))(4)].xH(2)O, where the divalent metal M in the framework may be Mg, Mn, Fe, Co, Ni, Cu, Zn, or Cd. A closely related crystalline material with a [Ca(CO(3))(2)(2-)](n) sodalite-like framework, but containing K(+) rather than Na(+), of composition [Ca(6)(CO(3))(12)(CH(6)N(3))(8)]K(3)[N(CH(3))(4)].3H(2)O was also isolated. All of these compounds were obtained under the simplest possible conditions from aqueous solution at room temperature, and their structures were determined by single-crystal X-ray diffraction. Pairs of guanidinium cations are associated with the hexagonal windows of the sodalite cages, alkali-metal cations are associated with their square windows, and N(CH(3))(4)(+) ions are located at their centers. Structures fall into two classes depending on the metal, M(II), in the framework. One type, the BC type (Im3m), comprising the compounds for which M(2+) = Ca(2+), Mn(2+), Cu(2+), and Cd(2+), has a body-centered cubic unit cell, while the second type, the FC type (Fd3c), for which M(2+) = Mg(2+), Fe(2+), Co(2+), Ni(2+), and Zn(2+), has a face-centered cubic unit cell with edges on the order of twice those of the BC structural type. The metal M in the BC structures has four close carbonate oxygen donors and four other more distant ones, while M in the FC structures has an octahedral environment consisting of two bidentate chelating carbonate ligands and two cis monodentate carbonate ligands.

The crystal structure of IgE Fc reveals an asymmetrically bent conformation.

The distinguishing structural feature of immunoglobulin E (IgE), the antibody responsible for allergic hypersensitivity, is the C epsilon 2 domain pair that replaces the hinge region of IgG. The crystal structure of the IgE Fc (constant fragment) at a 2.6-A resolution has revealed these domains. They display a distinctive, disulfide-linked Ig domain interface and are folded back asymmetrically onto the C epsilon 3 and C epsilon 4 domains, which causes an acute bend in the IgE molecule. The structure implies that a substantial conformational change involving C epsilon 2 must accompany binding to the mast cell receptor Fc epsilon RI. This may be the basis of the exceptionally slow dissociation rate of the IgE-Fc epsilon RI complex and, thus, of the ability of IgE to cause persistent allergic sensitization of mast cells.

IgE Fc structure and receptor interactions

IgE Fc structure and receptor interactions