scholarly journals Computational and NMR Conformational Analysis of Galactofuranoside Cycles Presented in Bacterial and Fungal Polysaccharide Antigens

2021 ◽  
Vol 8 ◽  
Author(s):  
Alexey G. Gerbst ◽  
Vadim B. Krylov ◽  
Nikolay E. Nifantiev
Keyword(s):  
Lactic Acid ◽  
Conformational Analysis ◽  
Experimental Evidence ◽  
Conformational Changes ◽  
Protein Interaction ◽  
Conformational Behavior ◽  
Hartree Fock ◽  
Conformational Preferences ◽  
Wide Range ◽  
Polysaccharide Antigens

Unlike pyranoside cycles which are generally characterized by strictly defined conformational preferences, furanosides are flexible and may adopt a wide range of available conformations. During our previous studies, conformational changes of galactofuranoside cycles upon total sulfation were described computationally, using a simple Hartree–Fock (HF) method, and principal conformers of the 5-membered galactose ring were revealed. However, in the case of more complex disaccharide structures, it was found that this method and the widely applied DFT-B3LYP produced results that deviated from experimental evidence. In this study, other DFT functionals (PBE0 and double hybrid B2PLYP) along with RI-MP2 are employed to study the conformational behavior of the galactofuranoside ring. Reinvestigation of galactofuranosides with a lactic acid substituent at O-3 revealed that changes in the orientation of lactic acid residue at O-3 might induce conformational changes of the furanoside cycle. Such findings are important for further modeling of carbohydrate–protein interaction.

Constant pH Molecular Dynamics Reveals How Proton Release Drives the Conformational Transition of a Transmembrane Efflux Pump

2017 ◽  
Author(s):  
Jana Shen ◽  
Zhi Yue ◽  
Helen Zgurskaya ◽  
Wei Chen
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Transmembrane Domain ◽  
Conformational Transition ◽  
Conformational Dynamics ◽  
Proton Release ◽  
Intrinsic Resistance ◽  
Constant Ph ◽  
Wide Range ◽  
Constant Ph Molecular Dynamics

AcrB is the inner-membrane transporter of E. coli AcrAB-TolC tripartite efflux complex, which plays a major role in the intrinsic resistance to clinically important antibiotics. AcrB pumps a wide range of toxic substrates by utilizing the proton gradient between periplasm and cytoplasm. Crystal structures of AcrB revealed three distinct conformational states of the transport cycle, substrate access, binding and extrusion, or loose (L), tight (T) and open (O) states. However, the specific residue(s) responsible for proton binding/release and the mechanism of proton-coupled conformational cycling remain controversial. Here we use the newly developed membrane hybrid-solvent continuous constant pH molecular dynamics technique to explore the protonation states and conformational dynamics of the transmembrane domain of AcrB. Simulations show that both Asp407 and Asp408 are deprotonated in the L/T states, while only Asp408 is protonated in the O state. Remarkably, release of a proton from Asp408 in the O state results in large conformational changes, such as the lateral and vertical movement of transmembrane helices as well as the salt-bridge formation between Asp408 and Lys940 and other sidechain rearrangements among essential residues.Consistent with the crystallographic differences between the O and L protomers, simulations offer dynamic details of how proton release drives the O-to-L transition in AcrB and address the controversy regarding the proton/drug stoichiometry. This work offers a significant step towards characterizing the complete cycle of proton-coupled drug transport in AcrB and further validates the membrane hybrid-solvent CpHMD technique for studies of proton-coupled transmembrane proteins which are currently poorly understood. <p><br></p>

pH-Dependent Thermal Stability of Vibrio cholerae L-asparaginase

2019 ◽  
Vol 26 (10) ◽  
pp. 743-750 ◽  
Author(s):  
Remya Radha ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Vibrio Cholerae ◽  
Conformational Changes ◽  
Kinetic Studies ◽  
Structural Features ◽  
Structure Stability ◽  
Kcal Mole ◽  
Scanning Calorimetry ◽  
Wide Range ◽  
Ph Dependent ◽  
Ph Range

Background:pH is one of the decisive macromolecular properties of proteins that significantly affects enzyme structure, stability and reaction rate. Change in pH may protonate or deprotonate the side group of aminoacid residues in the protein, thereby resulting in changes in chemical and structural features. Hence studies on the kinetics of enzyme deactivation by pH are important for assessing the bio-functionality of industrial enzymes. L-asparaginase is one such important enzyme that has potent applications in cancer therapy and food industry.Objective:The objective of the study is to understand and analyze the influence of pH on deactivation and stability of Vibrio cholerae L-asparaginase.Methods:Kinetic studies were conducted to analyze the effect of pH on stability and deactivation of Vibrio cholerae L-asparaginase. Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC) studies have been carried out to understand the pH-dependent conformational changes in the secondary structure of V. cholerae L-asparaginase.Results:The enzyme was found to be least stable at extreme acidic conditions (pH< 4.5) and exhibited a gradual increase in melting temperature from 40 to 81 °C within pH range of 4.0 to 7.0. Thermodynamic properties of protein were estimated and at pH 7.0 the protein exhibited ΔG37of 26.31 kcal mole-1, ΔH of 204.27 kcal mole-1 and ΔS of 574.06 cal mole-1 K-1.Conclusion:The stability and thermodynamic analysis revealed that V. cholerae L-asparaginase was highly stable over a wide range of pH, with the highest stability in the pH range of 5.0–7.0.

scholarly journals Relationship between the Stereocomplex Crystallization Behavior and Mechanical Properties of PLLA/PDLA Blends

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1851
Author(s):  
Hye-Seon Park ◽  
Chang-Kook Hong
Keyword(s):  
Mechanical Properties ◽  
Lactic Acid ◽  
Crystallization Behavior ◽  
Mechanical Analysis ◽  
X Ray Diffraction ◽  
Nucleation Agent ◽  
Scanning Calorimetry ◽  
Nucleation Sites ◽  
Wide Range ◽  
Degree Of Crystallization

Poly (l-lactic acid) (PLLA) is a promising biomedical polymer material with a wide range of applications. The diverse enantiomeric forms of PLLA provide great opportunities for thermal and mechanical enhancement through stereocomplex formation. The addition of poly (d-lactic acid) (PDLA) as a nucleation agent and the formation of stereocomplex crystallization (SC) have been proven to be an effective method to improve the crystallization and mechanical properties of the PLLA. In this study, PLLA was blended with different amounts of PDLA through a melt blending process and their properties were calculated. The effect of the PDLA on the crystallization behavior, thermal, and mechanical properties of PLLA were investigated systematically by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), polarized optical microscopy (POM), dynamic mechanical analysis (DMA), and tensile test. Based on our findings, SC formed easily when PDLA content was increased, and acts as nucleation sites. Both SC and homo crystals (HC) were observed in the PLLA/PDLA blends. As the content of PDLA increased, the degree of crystallization increased, and the mechanical strength also increased.

P0031AURINE METABOLOMICS: AN EMERGING TOOL FOR DISSECTING BIOLOGICAL ABERRATIONS UNDERLYING RENAL DYSFUNCTION IN BARDET-BIEDL SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Miriam Zacchia ◽  
Emanuela Marchese ◽  
Marianna Caterino ◽  
Margherita Ruoppolo ◽  
Giovambattista Capasso
Keyword(s):  
Lactic Acid ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
Metabolic Pathways ◽  
Healthy Subjects ◽  
Hexadecenoic Acid ◽  
Kidney Dysfunction ◽  
Bardet Biedl Syndrome ◽  
Wide Range

Abstract Background and Aims Bardet Biedl Syndrome (BBS) is a rare genetic disorder characterized by a wide range of organ dysfunction, including kidney disease. The severity of renal dysfunction is highly variable in this setting, ranging from tubular defects to the end stage renal disease, with poor genotype-phenotype correlation. Proteomics and metabolomics are powerful tools able to contribute to the better understanding of molecular basis of disease conditions. Our previous studies demonstrated that the urinary proteomic pattern of BBS patients differed from that of healthy subjects, with a set of deregulated proteins including cell adhesion and extracellular matrix organization proteins (1). The present study aims to characterize urine metabolomic profile of BBS patients, in order to identify both 1) potential disease biomarkers and 2) aberrant metabolic pathways underlying renal disease Method To this end, in the pilot study urine samples have been collected from 14 adult BBS patients and have been compared with healthy volunteers, using an untargeted strategy. In the confirmation study, 24 BBS patients with wide range of kidney dysfunction have been enrolled, and additional control groups, besides healthy subjects, were included: 1) age-gender-matched chronic kidney disease patients by other causes and 2) obese individuals. Results Several metabolites were de-regulated in BBS patients compared with normal subjects (lactic acid, glycolic acid,3-Hydroxypropionic acid, pyruvic acid, 3-hydroxyisobutyric acid, 2-ethyl-3-hydroxy-propionic acid, succinic acid, fumaric acid, erythropentonic acid, 2-hydroxyglutaric acid, 4-hydroxyphenyllactic acid, 3,4-pyridinedicarboxylic acid, retinoic acid, 4-hydroxyphenylacetic acid, palmitic acid, 9-Hexadecenoic acid, oleic acid and 9-Octadecenoic acid). The clusterization performed by MetaboAnalyst tool, revealed a possible deregulation of different metabolic pathways, including glycolysis, TCA cycle, pyruvate metabolism, lipids biosynthesis and glutamate metabolism (p-value &lt;0.01) (figure 1); some of these pathways were described as de-regulated in other ciliopathies (2). In the confirmation study (on-going studies) some metabolites, including lactic acid and intermediates of Krebs cycle, correlated with kidney dysfunction only in the BBS group. Conclusion These findings suggest that urine metabolomic fingerprint of BBS patients is different from that of healthy subjects and indicate a possible deregulation of several metabolic pathways; some urinary molecules correlated with kidney dysfunction only in BBS patients, suggesting the specificity of these results.

BIOASSAY OF ANTIGONADOTROPHIC SERA

1970 ◽  
Vol 63 (1) ◽  
pp. 150-160 ◽  
Author(s):  
P. Petrusz ◽  
C. Robyn ◽  
E. Diczfalusy ◽  
D. J. Finney
Keyword(s):  
Experimental Evidence ◽  
Bioassay Method ◽  
Wide Range

ABSTRACT Experimental evidence is presented indicating that the principle of additivity between gonadotrophic and antigonadotrophic activities which forms the basis of the previously proposed bioassay method for antigonadotrophic sera (Robyn et al. 1968) is valid for a wide range of hormone:antiserum ratios. From knowledge of the antigonadotrophic potency of an antiserum, it is possible to select an amount of antiserum which will completely neutralize a given gonadotrophic activity.

scholarly journals Experimental Evidence for Membrane-Mediated Protein-Protein Interaction

2010 ◽  
Vol 99 (7) ◽  
pp. L47-L49 ◽  
Author(s):  
Ignacio Casuso ◽  
Pierre Sens ◽  
Felix Rico ◽  
Simon Scheuring
Keyword(s):  
Experimental Evidence ◽  
Protein Interaction ◽  
Protein Protein Interaction

Raman spectroscopic study of conformational changes in the amorphous phase of poly(lactic acid) during deformation

Polymer ◽  
2004 ◽  
Vol 45 (12) ◽  
pp. 4241-4248 ◽  
Author(s):  
Xiaozhen Yang ◽  
Shuhui Kang ◽  
Yuning Yang ◽  
Kaoru Aou ◽  
Shaw Ling Hsu
Keyword(s):  
Lactic Acid ◽  
Spectroscopic Study ◽  
Amorphous Phase ◽  
Conformational Changes ◽  
Poly Lactic Acid ◽  
Raman Spectroscopic ◽  
Raman Spectroscopic Study

scholarly journals Structural and functional studies of pyruvate carboxylase regulation by cyclic di-AMP in lactic acid bacteria

2017 ◽  
Vol 114 (35) ◽  
pp. E7226-E7235 ◽  
Author(s):  
Philip H. Choi ◽  
Thu Minh Ngoc Vu ◽  
Huong Thi Pham ◽  
Joshua J. Woodward ◽  
Mark S. Turner ◽  
...  
Keyword(s):  
Binding Site ◽  
Conformational Changes ◽  
Pyruvate Carboxylase ◽  
Adenosine Monophosphate ◽  
Binding Mode ◽  
Functional Studies ◽  
Cellular Processes ◽  
Wide Range ◽  
A Site ◽  
Amp Inhibition

Cyclic di-3′,5′-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism inListeria monocytogenesby inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT) activities. We report here structural, biochemical, and functional studies on the inhibition ofLactococcus lactisPC (LlPC) by c-di-AMP. The compound is bound at the dimer interface of the CT domain, at a site equivalent to that in LmPC, although it has a distinct binding mode in the LlPC complex. This binding site is not well conserved among PCs, and only a subset of these bacterial enzymes are sensitive to c-di-AMP. Conformational changes in the CT dimer induced by c-di-AMP binding may be the molecular mechanism for its inhibitory activity. Mutations of residues in the binding site can abolish c-di-AMP inhibition. InL. lactis, LlPC is required for efficient milk acidification through its essential role in aspartate biosynthesis. The aspartate pool inL. lactisis negatively regulated by c-di-AMP, and high aspartate levels can be restored by expression of a c-di-AMP–insensitive LlPC. LlPC has high intrinsic catalytic activity and is not sensitive to acetyl-CoA activation, in contrast to other PC enzymes.

scholarly journals Synthesis and Properties of Nitrogen-Doped Carbon Quantum Dots Using Lactic Acid as Carbon Source

Materials ◽  
2022 ◽  
Vol 15 (2) ◽  
pp. 466
Author(s):  
Kaixin Chang ◽  
Qianjin Zhu ◽  
Liyan Qi ◽  
Mingwei Guo ◽  
Woming Gao ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Lactic Acid ◽  
Fluorescence Quenching ◽  
Functional Groups ◽  
Fluorescence Intensity ◽  
Carbon Quantum Dots ◽  
Nitrogen Doped ◽  
Ph Values ◽  
Wide Range ◽  
Nitrogen Doped Carbon

Nitrogen-doped carbon quantum dots (N-CQDs) were synthesized in a one-step hydrothermal technique utilizing L-lactic acid as that of the source of carbon and ethylenediamine as that of the source of nitrogen, and were characterized using dynamic light scattering, X-ray photoelectron spectroscopy ultraviolet-visible spectrum, Fourier-transformed infrared spectrum, high-resolution transmission electron microscopy, and fluorescence spectrum. The generated N-CQDs have a spherical structure and overall diameters ranging from 1–4 nm, and their surface comprises specific functional groups such as amino, carboxyl, and hydroxyl, resulting in greater water solubility and fluorescence. The quantum yield of N-CQDs (being 46%) is significantly higher than that of the CQDs synthesized from other biomass in literatures. Its fluorescence intensity is dependent on the excitation wavelength, and N-CQDs release blue light at 365 nm under ultraviolet light. The pH values may impact the protonation of N-CQDs surface functional groups and lead to significant fluorescence quenching of N-CQDs. Therefore, the fluorescence intensity of N-CQDs is the highest at pH 7.0, but it decreases with pH as pH values being either more than or less than pH 7.0. The N-CQDs exhibit high sensitivity to Fe3+ ions, for Fe3+ ions would decrease the fluorescence intensity of N-CQDs by 99.6%, and the influence of Fe3+ ions on N-CQDs fluorescence quenching is slightly affected by other metal ions. Moreover, the fluorescence quenching efficiency of Fe3+ ions displays an obvious linear relationship to Fe3+ concentrations in a wide range of concentrations (up to 200 µM) and with a detection limit of 1.89 µM. Therefore, the generated N-CQDs may be utilized as a robust fluorescence sensor for detecting pH and Fe3+ ions.

scholarly journals Cocrystals of Ethenzamide With 2-Nitrobenzoic Acid - Conformational Analysis, MD Simulations And DFT Investigations

2021 ◽  
Author(s):  
Y. Sheena Mary ◽  
Y. Shyma Mary ◽  
Razieh Razavi
Keyword(s):  
Hydrogen Bond ◽  
Conformational Analysis ◽  
Crystal Engineering ◽  
Energy Charge ◽  
Thermodynamic Characteristics ◽  
Md Simulations ◽  
Pharmaceutical Chemistry ◽  
Nitrobenzoic Acid ◽  
Wide Range ◽  
Stability Energy

Abstract In crystal engineering and pharmaceutical chemistry, cocrystals have a wide range of applications. Ethenzamide (EA) is found to form cocrystal with 2-nitrobenzoic acid (NBA). Geometry properties like stability energy, charge distribution, bond length, electronic properties and thermodynamic characteristics have been analyzed. The C-H…O hydrogen bond involves C-H of EA and oxygen of NBA. Configuration with the angle, N3-C4-C5-C6 gives the lowest energy conformation. Partition coefficient value suggests that EA-NBA has pharmaceutics behavior. RMSD values show the simulation’s relative stability and the complexes, remained stable throughout.

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