Side-chain Hydrogen Bonds Research Articles

The spectrum of factor XI deficiency in Southeast China: four recurrent variants can explain most of the deficiencies

BackgroundFactor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants.ResultsOf the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P < .001). Only nine patients experienced mild bleeding, including one partially defective patient and eight severely defective patients. The majority of patients were referred for preoperative screenings (n = 22) and checkups (n = 14). Genetic analysis revealed that 90% of the patients had genetic defects, with 2, 16, and 19 cases of heterozygous, homozygous, and compound heterozygous patients, respectively. Seventeen variants were detected in the F11 gene (6 novel), including eleven missense variants, four nonsense variants, and two small deletions scattered throughout the F11. Of the 11 missense variants, six have not yet been studied for in vitro expression. Protein modeling analyses indicated that all of these variants disrupted local structural stability by altering side-chain orientation and hydrogen bonds. Nine variants, consisting of three missense and six null variants, were detected with a frequency of two or more. The highest allele frequency was observed in p.Q281* (21.25%), p.W246* (17.50%), p.Y369* (12.50%), and p.L442Cfs*8 (12.50%). The former two were variants specific to East Asia, while the remaining two were southeast China-specific variants.ConclusionOur population-based cohort demonstrated that no correlation between the level of FXI activity and the bleeding severity in FXI deficiency. Additionally, the prevalence of FXI deficiency may have been underestimated. The nonsense p.Q281* was the most common variant in southeast China, suggesting a possible founder effect.

All-Atom Molecular Dynamics Simulations of Uncharged Linear Polymer Bottlebrushes: Effect of the Brush Sizes and the Number of Side-Chain Monomers.

Bottlebrush polymers (BBPs), characterized by grafted polymer side chains on linear backbone polymer chain, have emerged as a unique and versatile class of macromolecules with extensive applications in the fields of material science, electronics, battery materials, self-healing technology, etc. In this paper, we employ all-atom molecular dynamics (MD) simulations to present a comprehensive study of poly(methyl methacrylate)-g-poly(2-ethyl-2-oxazoline) (PMMA-g-PEtOx) BBP and its structural and hydration properties for varying number of backbone monomers (NBB) and side chain monomers (NSC), as well as properties of water molecules supported by the BBP. We find that the radius of gyration follows a scaling of Rg ∼NSC0.36 for smaller grafts and Rg ∼ NSC0.52-0.58 for longer grafts. We also find that the overall shape of the bottlebrush goes from a rod to sphere-like shape with the increase in NSC. Both the hydration per side chain monomer and hydrogen bonds (HBs) per oxygen and nitrogen of the side chain monomer reduce with an increase in NSC, caused by a corresponding enhancement in localization of the side chain monomers in the interior of the BBP. Furthermore, steric influences ensure the number of water-oxygen HBs is much more than the number of water-nitrogen HBs (with oxygen and nitrogen atoms belonging to the monomer side chains). Also, the BBP-supported water molecules demonstrate two distinctly ordered domains with one more structured and one less structured. The more structured domain disappears with an increase in NSC that causes more side chain monomers to localize in the interior of the BBPs. Finally, we observe that despite the highly negative partial charges of the oxygen and nitrogen atoms (of the side chain monomers), the dipole orientation distributions of water molecules around these atoms exhibit the presence of a neutral environment rather than an anionic environment. Overall, we anticipate that our study will generate significant interest in probing the various BBP systems in greater atomistic detail.

Physically crosslinked polyacrylates by quadruple hydrogen bonding side chains.

Dynamic polymer materials can be obtained by introducing supramolecular interactions between the polymer chains. Here we report on the preparation and mechanical properties of poly(methyl acrylate) (PMA) and poly(n-butyl acrylate) (PBA) funcionalized with ureidopyrimidinone (UPy) in the side chains. In contrast to the traditional UPy with a methyl group, the selected UPy motif contained a branched alkyl side chain, which enhances solubility, compatibility with the polymer matrix and potentially prevents stacking of UPy dimers. Low molar mass PMA and PBA were synthesized via Cu(0)-mediated radical polymerization and allyl bonds were introduced with different degrees of functionalization by stoichiometrically controlled transesterification with allyl alcohol. The allyl esters served as functional handles for UPy attachment via UV-initiated radical thiol-ene coupling. The PMA-UPy materials displayed a more glassy appearance, in contrast to the rubbery PBA-UPy polymer networks, associated to its higher glass transition temperature. The mechanical properties of the resulting hydrogen bonded polymer networks were assessed by thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical thermal analysis and tensile testing, followed by rheological analysis of the network dynamics. Furthermore, the effect of associative groups on the linear viscoelastic response is discussed based on a modified sticky Rouse model indicating the absence of significant aggregation or phase separation of the UPY units.

The Role of Asn11 in Catalysis by Triosephosphate Isomerase.

Four catalytic amino acids at triosephosphate isomerase (TIM) are highly conserved: N11, K13, H95, and E167. Asparagine 11 is the last of these to be characterized in mutagenesis studies. The ND2 side chain atom of N11 is hydrogen bonded to the O-1 hydroxyl of enzyme-bound dihydroxyacetone phosphate (DHAP), and it sits in an extended chain of hydrogen-bonded side chains that includes T75' from the second subunit. The N11A variants of wild-type TIM from Trypanosoma brucei brucei (TbbTIM) and Leishmania mexicana (LmTIM) undergo dissociation from the dimer to monomer under our assay conditions. Values of Kas = 8 × 103 and 1 × 106 M-1, respectively, were determined for the conversion of monomeric N11A TbbTIM and LmTIM into their homodimers. The N11A substitution at the variant of LmTIM previously stabilized by the E65Q substitution gives the N11A/E65Q variant that is stable to dissociation under our assay conditions. The X-ray crystal structure of N11A/E65Q LmTIM shows an active site that is essentially superimposable on that for wild-type TbbTIM, which also has a glutamine at position 65. A comparison of the kinetic parameters for E65Q LmTIM and N11A/E65Q LmTIM-catalyzed reactions of (R)-glyceraldehyde 3-phosphate (GAP) and (DHAP) shows that the N11A substitution results in a (13-14)-fold decrease in kcat/Km for substrate isomerization and a similar decrease in kcat for DHAP but only a 2-fold decrease in kcat for GAP.

Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro

In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like protease (3CLpro) can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.50 Å resolution crystal structure of 3CLpro C145S bound to NEMO226–234 reveals subsites that tolerate a range of viral and host substrates through main chain hydrogen bonds while also enforcing specificity using side chain hydrogen bonds and hydrophobic contacts. Machine learning- and physics-based computational methods predict that variation in key binding residues of 3CLpro-NEMO helps explain the high fitness of SARS-CoV-2 in humans. We posit that cleavage of NEMO is an important piece of information to be accounted for, in the pathology of COVID-19.

Study of the microstructure and oxidation characteristics of residual coal in deep mines

Residual coal is prone to spontaneous combustion under the influence of high ground temperature, and the risk increases with mining depth. This results in gradual increases in smoke and dust emissions, which seriously affect the ecological and geological environment of the mining area. To avoid spontaneous combustion of the residual coal, protect the resources and ecology of mining areas, and investigate the influence of the deep thermal environment on the microstructure and oxidation properties of coal, the pore evolution characteristics and functional group migration of coal in a thermal environment were studied by N2 adsorption and infrared spectroscopy. A temperature-programmed test system was used to simulate the low-temperature oxidation process occurring in deep coal seams, and the heat release characteristics and oxidation kinetic parameters of the index gas were calculated. The experimental results revealed that the pore oxygen storage capacities and coal oxygen contact areas of residual coal in deep mines are larger than those of coal in shallow seams. As the preheating temperature is increased, the rates of CO and CO2 production and the amount of oxygen consumed in oxidation of heat-treated coal increase. The crossing point temperature (CPT) of heat-treated coal decreases. The deep thermal environment accelerates the rate of condensation decomposition of the aliphatic hydrocarbon groups in coal and fracture of side chain hydrogen bonds connecting strong electron-absorbing groups, which increases the exothermic intensity of the oxidation process. The reaction trigger temperatures for aliphatic hydrocarbon groups, peroxyl radicals, associative hydrogen bonds and other active groups in coal are different. With increasing ambient temperature, the types of active groups in coal increase, and the contents accumulate. With an increase in the deep geothermal temperature, the oxidation activity of coal is enhanced, and the coal is more prone to spontaneous combustion. These research results provide a theoretical reference for deep coal clean mining and prevention of spontaneous combustion disasters and have a potential guiding role in environmental protection and ecological improvement of deep mining areas.

Structure and Carbohydrate Recognition by the Nonmitogenic Lectin Horcolin.

Lectins are sugar-binding proteins that have shown considerable promise as antiviral agents because of their ability to interact with envelope glycoproteins present on the surface of viruses such as HIV-1. However, their therapeutic potential has been compromised by their mitogenicity that stimulates uncontrolled division of T-lymphocytes. Horcolin, a member of the jacalin family of lectins, tightly binds the HIV-1 envelope glycoprotein gp120 and neutralizes HIV-1 particles but is nonmitogenic. In this report, we combine X-ray crystallography and NMR spectroscopy to obtain atomic-resolution insights into the structure of horcolin and the molecular basis for its carbohydrate recognition. Each protomer of the horcolin dimer adopts a canonical β-prism I fold with three Greek key motifs and carries two carbohydrate-binding sites. The carbohydrate molecule binds in a negatively charged pocket and is stabilized by backbone and side chain hydrogen bonds to conserved residues in the ligand-binding loop. NMR titrations reveal a two-site binding mode and equilibrium dissociation constants for the two binding sites determined from two-dimensional (2D) lineshape modeling are 4-fold different. Single-binding-site variants of horcolin confirm the dichotomy in binding sites and suggest that there is allosteric communication between the two sites. An analysis of the horcolin structure shows a network of hydrogen bonds linking the two carbohydrate-binding sites directly and through a secondary binding site, and this coupling between the two sites is expected to assume importance in the interaction of horcolin with high-mannose glycans found on viral envelope glycoproteins.

A naturally occurring point mutation in the hyaluronidase gene (hysA1) of Staphylococcus aureus UAMS-1 results in reduced enzymatic activity.

Hyaluronic acid is a high-molecular-weight polysaccharide that is widely distributed in animal tissues. Bacterial hyaluronidases degrade hyaluronic acid as secreted enzymes and have been shown to contribute to infection. Staphylococcus aureus UAMS-1 is a clinical isolate that codes for two hyaluronidases (hysA1 and hysA2). Previous research has shown the presence of a full-length HysA1 protein from the S. aureus UAMS-1 strain with no evidence of enzymatic activity. In this study, the coding and upstream promoter regions of hysA1 from the S. aureus UAMS-1 strain were cloned, sequenced, and compared to the hysA1 gene from the S. aureus Sanger 252 strain. A single base change resulting in an E480G amino acid change was identified in the hysA1 gene from the S. aureus UAMS-1 strain when compared to the hysA1 gene from S. aureus Sanger 252. A plasmid copy of hysA1 from S. aureus Sanger 252 transduced into an S. aureus UAMS-1 hysA2 deletion mutant strain restored near wild-type levels of enzymatic activity. Homology modeling of the HysA1 hyaluronidase was performed with SWISS-MODEL using hyaluronidase from Streptococcus pneumoniae as the template, followed by a series of structural analyses using PyMOL, PLIP, PDBsum, and HOPE servers. This glutamic acid is highly conserved among hyaluronidases from Staphylococcus and other gram-positive bacteria. A series of structural analyses suggested that Glu-480 in HysA1 is critically responsible for maintaining the structural and functional ensemble of the catalytic and tunnel-forming residues, which are essential for enzyme activity. The missense mutation of Glu-480 to Gly introduces a loss of side chain hydrogen bond interactions with key residues Arg-360 and Arg-364, which are responsible for the tunnel topology, resulting in displacement of the substrate from an ideal position for catalysis through a localized conformational change of the active site. There is a high degree of relatedness among several gram-positive bacterial hyaluronidases; the loss of enzymatic activity of HysA1 in the S. aureus UAMS-1 strain is most likely caused by the mutation identified in our study. The role of hyaluronidase in staphylococcal infection and the redundancy of this gene are yet to be determined.

Main‐Side Chain Hydrogen Bonding‐Based Self‐Healable Polyurethane with Highly Stretchable, Excellent Mechanical Properties for Self‐Healing Acid–Base Resistant Coating

Developing an autonomous self-healing polyurethane (PU) elastomer with excellent mechanical properties and high ductility has attracted increasing attention. Nowadays, the synthesis of elastomers with excellent mechanical properties and rapid self-healing at room temperature faces a huge challenge. Herein, This work reports a new supramolecular PU with excellent mechanical properties and rapid self-healing at room temperature through the introduction of T-type chain extender into the supramolecular polymer chain. The introduction of T-chain extender can be used to enhance the mechanical strength of PU, and the multiple hydrogen bonds on the side-chain provide theoretical support for the rapid self-healing ability of PU. Maximum stress of the synthesized PU can reach 3.4 ± 0.15 Mpa, and maximum elongation at break can reach 3200% ± 160%. Due to flexibility and re-constructability of side-chain hydrogen bonds, PU stress repair efficiency can reach 96.7%, and can be self-healing scratches rapidly and effectively at room temperature. The mechanical properties and self-healing properties of PU can be adjusted by the content of T-type chain extender. The PU is applied to the metal surface coating, which has excellent acid-base resistance, bond strength up to 2.9 ± 0.1 Mpa, and the ability to eliminate local damage on the coating surface quickly at room temperature.

Nanotechnology-based approaches for targeting and delivery of drugs via Hexakis (m-PE) macrocycles

Hexakis (m-phenylene ethynylene) (m-PE) macrocycles, with aromatic backbones and multiple hydrogen-bonding side chains, had a very high propensity to self-assemble via H-bond and π–π stacking interactions to form nanotubular structures with defined inner pores. Such stacking of rigid macrocycles is leading to novel applications that enable the researchers to explored mass transport in the sub-nanometer scale. Herein, we performed density functional theory (DFT) calculations to examine the drug delivery performance of the hexakis dimer as a novel carrier for doxorubicin (DOX) agent in the chloroform and water solvents. Based on the DFT results, it is found that the adsorption of DOX on the carrier surface is typically physisorption with the adsorption strength values of − 115.14 and − 83.37 kJ/mol in outside and inside complexes, respectively, and so that the essence of the drug remains intact. The negative values of the binding energies for all complexes indicate the stability of the drug molecule inside and outside the carrier's cavities. The energy decomposition analysis (EDA) has also been performed and shown that the dispersion interaction has an essential role in stabilizing the drug-hexakis dimer complexes. To further explore the electronic properties of dox, the partial density of states (PDOS and TDOS) are calculated. The atom in molecules (AIM) and Becke surface (BS) methods are also analyzed to provide an inside view of the nature and strength of the H-bonding interactions in complexes. The obtained results indicate that in all studied complexes, H-bond formation is the driving force in the stabilization of these structures, and also chloroform solvent is more favorable than the water solution. Overall, our findings offer insightful information on the efficient utilization of hexakis dimer as drug delivery systems to deliver anti-cancer drugs.

Exploring the Proton-Transfer Mechanism in Hv1 by Multi-Scale Simulations

The Hv1 proton channel is expressed in a broad range of eukaryotic cells, where its chief physiological role is to mediate proton efflux. Hv1 is a potential target for the development of drugs to treat human pathologies, including breast cancer and ischemic stroke. Similar to other voltage sensor (VS) domain-containing proteins, Hv1 gating is controlled by changes in membrane potential. The H+ permeation pathway in Hv1 is formed by an hourglass-shaped hydrated VS central crevice, with several conserved hydrophobic residues forming a central bottleneck region. Although specific residues have been identified as potential sites for proton transfer by explicit side chain ionization, almost all neutralizations of ‘selectivity filter’ residues D112, R211, and other highly conserved ‘gating-charge’ or ‘counter-charge’ residues have so far failed to abolish H+ currents on Hv1. An alternative H+ transfer mechanism, in which VS-resident water molecules form a water wire, has not been ruled out. To investigate structural constraints on possible water wire formation in Hv1 we conducted classical molecular dynamics simulations followed by mixed quantum-mechanics/molecular-mechanics (QM/MM) simulations on a new, experimentally constrained activated-state Hv1 model structure. The calculations will allow us to focus on how dynamics in the bottleneck region that envelops a D112-R211 salt bridge impact water and side chain hydrogen bond network structures, possible water wire formation, and energetic barriers to proton migration.

Effect and regulation of the secondary structure of synthetic poly(&amp;alpha;-amino acid) based on ring-opening polymerization

Protein is one of the most important components that constitute the organism. A unique property of protein is the adoption of highly ordered secondary structure formed by hydrogen bond. Poly(α-amino acid)s are protein mimics that also present hydrogen bonds in the backbone and similarly adopt secondary structure (e.g., α-helix and β-sheet). In addition, poly(α-amino acid)s usually possess desired biocompatibility and biodegradability. Therefore, they have demonstrated extensive utilities in the biological fields. In this review, we firstly introduced the formation mechanism of ordered secondary structure of poly(α-amino acid)s. In general, α-helix exhibits rigid rod-like structure due to the intramolecular hydrogen bonds, while β-sheet structure is mainly formed based on the intermolecular hydrogen bonds. The polymerization degree of poly(α-amino acid)s that form β-sheet is often lower than that of poly(α-amino acid)s with α-helix structure. Besides, the formation of the random coil structure is often due to the distortion of the backbone. Then, we discussed the impact of side-chain functionalization on the secondary structure and introduced the existing approaches in modulating the secondary structure, such as controlling the electrostatic interaction, polarity, and hydrogen bonds. By maintaining a separation distance of more than 11 σ-bond between the backbone and side charged groups, the poly(α-amino acid) could adopt α-helical structure due to the diminished interference with the backbone hydrogen bonds. The electrostatic interaction among the side chains disturbs the hydrogen bonding, thereby destabilizing the α-helical structure. For instance, the conformation of light-responsive helical poly(α-amino acid)s can transform into random coil due to side-chain electrostatic attraction after irradiation, while random coil-to-helix transition of zwitterionic poly(α-amino acid)s was achieved via elimination of the side-chain electrostatic interaction in response to phosphatase or acidic pH. In addition, the increased polarity of the side chains of polycysteine and poly(homocysteine) derivatives upon oxidation can also realize the order-order and order-disorder transition of the secondary structure. Moreover, the conformation of poly(α-amino acid)s with triazole groups in the side chains can be transformed from random coil to α-helix when the pH value is decreased, mainly due to the change in the side-chain hydrogen bond pattern. We further summarized the impact of secondary structure on the bio-applications of poly(α-amino acid)s, including cell penetration, gene delivery, anti-microbial therapy, self-assembly, and protein modification. Normally, α-helical conformation features strong membrane penetration and thus α-helical poly(α-amino acid)s can mediate effective gene transfection. pH-responsive, coil-helix transitional poly(α-amino acid)s can allow helix formation in the acidic endolysosomes to specifically penetrate endolysosomal membranes, while light-triggered distortion of the helix at the post-transfection state can diminish the long-term materials toxicity. α-Helical poly(α-amino acid)s with well-tailored structure can also enable potent anti-microbial efficiency by disruption bacterial membranes, and conformation transitionable poly(α-amino acid)s can mediate potent yet selective killing of bacteria upon coil-to-helix transition in response to over-produced phosphatases in infected sites or acidic pH in the stomach. In addition, the secondary structure also has a huge impact on the self-assembly behavior of poly(α-amino acid)s or the pharmacological properties of protein drugs modified with poly(α-amino acid)s. Therefore, the research on the secondary structure and function of poly(α-amino acid)s renders great inspiration for its further application.

Stability of Human Serum Amyloid A Fibrils.

In systemic amyloidosis, serum amyloid A (SAA) fibril deposits cause widespread damages to tissues and organs that eventually may lead to death. A therapeutically intervention therefore has either to dissolve these fibrils or inhibit their formation. However, only recently has the human SAA fibril structure been resolved at a resolution that is sufficient for development of drug candidates. Here, we use molecular dynamic simulations to probe the factors that modulate the stability of this fibril model. Our simulations suggest that fibril formation starts with the stacking of two misfolded monomers into metastable dimers, with the stacking depending on the N-terminal amyloidogenic regions of different chains forming anchors. The resulting dimers pack in a second step into a 2-fold two-layer tetramer that is stable enough to nucleate fibril formation. The stability of the initial dimers is enhanced under acidic conditions by a strong salt bridge and side-chain hydrogen bond network in the C-terminal cavity (residues 23-51) but is not affected by the presence of the disordered C-terminal tail.

The complex impedance, dielectric relaxation, complex modulus and photoluminescence studies of pure and L-Methionine doped ammonium dihydrogen phosphate

The ammonium dihydrogen phosphate (ADP) is one of the pioneer nonlinear optical materials utilized for frequency doubling experiment of Nd:YAG laser. The amino acids are bifunctional material that contains the weak hydrogen bonded side chain. In the present study the authors have studied influence of L-Methionine on structural, photoluminescence and a.c.electrical properties of ADP. The powder XRD study suggested tetragonal structure symmetry and single phasic nature of all the samples. The photoluminescence is confirmed existence of the Self Trapped Excitons. The Correlation Barrier Hopping and Nonoverllaping Small Polaron Tunnelling kind of conduction mechanism is observed in present system. The Complex Impedance and Complex Modulus spectroscopy have suggested presence of grain and grain boundary within the samples.

A three-dimensional potential of mean force to improve backbone and sidechain hydrogen bond geometry in Xplor-NIH protein structure determination.

We introduce a new hydrogen bonding potential of mean force generated from high-quality crystal structures for use in Xplor-NIH structure calculations. This term applies to hydrogen bonds involving both backbone and sidechain atoms. When used in structure refinement calculations of 10 example protein systems with experimental distance, dihedral and residual dipolar coupling restraints, we demonstrate that the new term has superior performance to the previously developed hydrogen bonding potential of mean force used in Xplor-NIH.

Biochemical insights into a novel thermo/organo tolerant bilirubin oxidase from Thermosediminibacter oceani and its application in dye decolorization

Abstract Higher activity and stability at neutral pH and tolerance toward anions have made bilirubin oxidases (BODs) proper candidates for industrial utilizations. A putative BOD from Thermosediminibacter oceani (ToBOD) exhibited high stability over a pH range of 3.5–10.0 after heterologous expression and purification. The optimal temperature for the enzyme activity was 75 °C. ToBOD displayed a high thermostability with a half-life of 180 min at 70 °C and 120 min at 80 °C, respectively. Km and Kcat values were 126.5 μM and 130.9 S−1 for ABTS, 19.6 μM and 72.5 S−1 for SGZ, and 31.2 μM and 76.2 S−1 for unconjugated bilirubin, respectively. ToBOD showed tolerance to 10% and 50% (v/v) of water-miscible organic solvents and Triton X-100 as a non-ionic surfactant. In the presence of ABTS as the mediator, ToBOD decolorized malachite green (MG) and Congo red (CR) dyes at a rate of about 63% and 71%, respectively in 2 h. Decolorization was improved within 4 h at a rate of 86% and 89% for MG and CR, respectively. Structural analyses of ToBOD showed that lower folding heat capacity, folding enthalpy, folding free energy, and side-chain hydrogen bonds have a correlation with in vitro biochemical properties.

Crystal structures of the naturally fused CS and cytochrome b5 reductase (b5R) domains of Ncb5or reveal an expanded CS fold, extensive CS-b5R interactions and productive binding of the NAD(P)+ nicotinamide ring.

Ncb5or (NADH-cytochrome b5 oxidoreductase), a cytosolic ferric reductase implicated in diabetes and neurological diseases, comprises three distinct domains, cytochrome b5 (b5) and cytochrome b5 reductase (b5R) domains separated by a CHORD-Sgt1 (CS) domain, and a novel 50-residue N-terminal region. Understanding how interdomain interactions in Ncb5or facilitate the shuttling of electrons from NAD(P)H to heme, and how the process compares with the microsomal b5 (Cyb5A) and b5R (Cyb5R3) system, is of interest. A high-resolution structure of the b5 domain (PDB entry 3lf5) has previously been reported, which exhibits substantial differences in comparison to Cyb5A. The structural characterization of a construct comprising the naturally fused CS and b5R domains with bound FAD and NAD+ (PDB entry 6mv1) or NADP+ (PDB entry 6mv2) is now reported. The structures reveal that the linker between the CS and b5R cores is more ordered than predicted, with much of it extending the β-sandwich motif of the CS domain. This limits the flexibility between the two domains, which recognize one another via a short β-sheet motif and a network of conserved side-chain hydrogen bonds, salt bridges and cation-π interactions. Notable differences in FAD-protein interactions in Ncb5or and Cyb5R3 provide insight into the selectivity for docking of their respective b5 redox partners. The structures also afford a structural explanation for the unusual ability of Ncb5or to utilize both NADH and NADPH, and represent the first examples of native, fully oxidized b5R family members in which the nicotinamide ring of NAD(P)+ resides in the active site. Finally, the structures, together with sequence alignments, show that the b5R domain is more closely related to single-domain Cyb5R proteins from plants, fungi and some protists than to Cyb5R3 from animals.

Opposing Effects of Side-Chain Flexibility and Hydrogen Bonding on the Thermal, Mechanical, and Rheological Properties of Supramolecularly Cross-Linked Polyesters

We report the design of a series of polyesters containing pendant secondary amide groups to probe the cumulative effects of hydrogen bonding and chain flexibility on their thermal, mechanical, and ...

Layered conductive polymer-inorganic anion network for high-performance ultra-loading capacitive electrodes

Conducting layered capacitive materials that utilize interlayer space to store charges usually exhibit higher areal and volumetric capacitive performance than porous carbons as a result of the bulk storage mechanism. Here, an organic-inorganic hybrid conducting layered material is designed through a ‘bottom-up’ strategy, and is synthesized facilely using a ‘one-pot’ approach. This material consists of periodically stacked nanosheets with a large lamellar period of 11.81 Å. It is postulated that each nanosheet is composed of parallel oriented fully oxidized polyaniline (pernigraniline) molecular chains that are crosslinked by monomeric/oligomeric protonated tungstate molecules, both of which are self-organized through multiple side-chain hydrogen bonds. The binder-free high-loading electrodes made from this material can deliver high volumetric and areal capacitance in neutral electrolyte, along with moderate gravimetric capacitance. As exemplified, a 40 mg cm−2 binder-free electrode achieves an areal capacitance of 4.62 F cm−2 and a volumetric capacitance of 219.4 F cm−3 at 1 mA cm−2.

Dielectric relaxation, protonic defect, conductivity mechanisms, complex impedance and modulus spectroscopic studies of pure and L-threonine-doped ammonium dihydrogen phosphate

Ammonium dihydrogen phosphate (ADP) has a wide range of applications in integrated and nonlinear optics. The dopant-like L-threonine has hydrogen-bonded side chain that causes defects in ADP. The pure and L-threonine-doped ADP crystals are grown using slow evaporation technique. The powder XRD patterns show the single-phase nature of pure and doped ADP. The dielectric constant and dielectric loss have shown the usual behaviour with respect to frequency and temperature. The protonic conduction is prevailing for electric transport, and from Jonscher’s plot, the correlation barrier hopping (CBH) and non-overlapping small polaron tunnelling (NSPT) conduction mechanism is confirmed. The Nyquist plot and modulus spectra show the presence of grain and grain boundary. The stretch exponent exhibits non-Debye-type relaxation. The activation energy of relaxation time for all samples is calculated. The modulus master curve and variation of Z″ and M″ versus angular frequency confirmed the proposed conduction. The nonlinear optical counterpart is in accordance with dielectric results.