International Journal of Molecular Sciences

265 KiB

Open AccessReview

Protease Inhibitors from Plants with Antimicrobial Activity

by Jin-Young Kim, Seong-Cheol Park, Indeok Hwang, Hyeonsook Cheong, Jae-Woon Nah, Kyung-Soo Hahm and Yoonkyung Park

Int. J. Mol. Sci. 2009, 10(6), 2860-2872; https://doi.org/10.3390/ijms10062860 - 23 Jun 2009

Cited by 183 | Viewed by 22971

Abstract

Antimicrobial proteins (peptides) are known to play important roles in the innate host defense mechanisms of most living organisms, including plants, insects, amphibians and mammals. They are also known to possess potent antibiotic activity against bacteria, fungi, and even certain viruses. Recently, the [...] Read more.

Antimicrobial proteins (peptides) are known to play important roles in the innate host defense mechanisms of most living organisms, including plants, insects, amphibians and mammals. They are also known to possess potent antibiotic activity against bacteria, fungi, and even certain viruses. Recently, the rapid emergence of microbial pathogens that are resistant to currently available antibiotics has triggered considerable interest in the isolation and investigation of the mode of action of antimicrobial proteins (peptides). Plants produce a variety of proteins (peptides) that are involved in the defense against pathogens and invading organisms, including ribosome-inactivating proteins, lectins, protease inhibitors and antifungal peptides (proteins). Specially, the protease inhibitors can inhibit aspartic, serine and cysteine proteinases. Increased levels of trypsin and chymotrypsin inhibitors correlated with the plants resistance to the pathogen. Usually, the purification of antimicrobial proteins (peptides) with protease inhibitor activity was accomplished by salt-extraction, ultrafiltration and C₁₈ reverse phase chromatography, successfully. We discuss the relation between antimicrobial and anti-protease activity in this review. Protease inhibitors from plants potently inhibited the growth of a variety of pathogenic bacterial and fungal strains and are therefore excellent candidates for use as the lead compounds for the development of novel antimicrobial agents. Full article

(This article belongs to the Special Issue Antimicrobial Agents)

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650 KiB

Open AccessArticle

Inactivation and Unfolding of the Hyperthermophilic Inorganic Pyrophosphatase from Thermus thermophilus by Sodium Dodecyl Sulfate

by Hang Mu, Sheng-Mei Zhou, Yong Xia, Hechang Zou, Fanguo Meng and Yong-Bin Yan

Int. J. Mol. Sci. 2009, 10(6), 2849-2859; https://doi.org/10.3390/ijms10062849 - 23 Jun 2009

Cited by 9 | Viewed by 10971

Abstract

Inorganic pyrophosphatase (PPase, EC 3.6.1.1) is an essential constitutive enzyme for energy metabolism and clearance of excess pyrophosphate. In this research, we investigated the sodium dodecyl sulfate (SDS)-induced inactivation and unfolding of PPase from Thermus thermophilus (T-PPase), a hyperthermophilic enzyme. The results indicated [...] Read more.

Inorganic pyrophosphatase (PPase, EC 3.6.1.1) is an essential constitutive enzyme for energy metabolism and clearance of excess pyrophosphate. In this research, we investigated the sodium dodecyl sulfate (SDS)-induced inactivation and unfolding of PPase from Thermus thermophilus (T-PPase), a hyperthermophilic enzyme. The results indicated that like many other mesophilic enzymes, T-PPase could be fully inactivated at a low SDS concentration of 2 mM. Using an enzyme activity assay, SDS was shown to act as a mixed type reversible inhibitor, suggesting T-PPase contained specific SDS binding sites. At high SDS concentrations, T-PPase was denatured via a two-state process without the accumulation of any intermediate, as revealed by far-UV CD and intrinsic fluorescence. A comparison of the inactivation and unfolding data suggested that the inhibition might be caused by the specific binding of the SDS molecules to the enzyme, while the unfolding might be caused by the cooperative non-specific binding of SDS to T-PPase. The possible molecular mechanisms underlying the mixed type inhibition by SDS was proposed to be caused by the local conformational changes or altered charge distributions. Full article

(This article belongs to the Section Biochemistry)

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221 KiB

Open AccessReview

Folding Mechanism of Beta-Hairpin Trpzip2: Heterogeneity, Transition State and Folding Pathways

by Yi Xiao, Changjun Chen and Yi He

Int. J. Mol. Sci. 2009, 10(6), 2838-2848; https://doi.org/10.3390/ijms10062838 - 22 Jun 2009

Cited by 31 | Viewed by 12493

Abstract

We review the studies on the folding mechanism of the β-hairpin tryptophan zipper 2 (trpzip2) and present some additional computational results to refine the picture of folding heterogeneity and pathways. We show that trpzip2 can have a two-state or a multi-state folding pattern, [...] Read more.

We review the studies on the folding mechanism of the β-hairpin tryptophan zipper 2 (trpzip2) and present some additional computational results to refine the picture of folding heterogeneity and pathways. We show that trpzip2 can have a two-state or a multi-state folding pattern, depending on whether it folds within the native basin or through local state basins on the high-dimensional free energy surface; Trpzip2 can fold along different pathways according to the packing order of tryptophan pairs. We also point out some important problems related to the folding mechanism of trpzip2 that still need clarification, e.g., a wide distribution of the computed conformations for the transition state ensemble. Full article

(This article belongs to the Special Issue Protein Folding 2009)

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Open AccessArticle

Calculation of the Aqueous Thermodynamic Properties of Citric Acid Cycle Intermediates and Precursors and the Estimation of High Temperature and Pressure Equation of State Parameters

by Peter Dalla-Betta and Mitchell Schulte

Int. J. Mol. Sci. 2009, 10(6), 2809-2837; https://doi.org/10.3390/ijms10062809 - 22 Jun 2009

Cited by 13 | Viewed by 13436

Abstract

The citric acid cycle (CAC) is the central pathway of energy transfer for many organisms, and understanding the origin of this pathway may provide insight into the origins of metabolism. In order to assess the thermodynamics of this key pathway for microorganisms that [...] Read more.

The citric acid cycle (CAC) is the central pathway of energy transfer for many organisms, and understanding the origin of this pathway may provide insight into the origins of metabolism. In order to assess the thermodynamics of this key pathway for microorganisms that inhabit a wide variety of environments, especially those found in high temperature environments, we have calculated the properties and parameters for the revised Helgeson-Kirkham-Flowers equation of state for the major components of the CAC. While a significant amount of data is not available for many of the constituents of this fundamental pathway, methods exist that allow estimation of these missing data. Full article

(This article belongs to the Special Issue Origin of Life)

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Open AccessArticle

Lattice Strain Due to an Atomic Vacancy

by Shidong Li, Michael S. Sellers, Cemal Basaran, Andrew J. Schultz and David A. Kofke

Int. J. Mol. Sci. 2009, 10(6), 2798-2808; https://doi.org/10.3390/ijms10062798 - 19 Jun 2009

Cited by 43 | Viewed by 13887

Abstract

Volumetric strain can be divided into two parts: strain due to bond distance change and strain due to vacancy sources and sinks. In this paper, efforts are focused on studying the atomic lattice strain due to a vacancy in an FCC metal lattice [...] Read more.

Volumetric strain can be divided into two parts: strain due to bond distance change and strain due to vacancy sources and sinks. In this paper, efforts are focused on studying the atomic lattice strain due to a vacancy in an FCC metal lattice with molecular dynamics simulation (MDS). The result has been compared with that from a continuum mechanics method. It is shown that using a continuum mechanics approach yields constitutive results similar to the ones obtained based purely on molecular dynamics considerations. Full article

(This article belongs to the Special Issue Composite Materials)

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104 KiB

Open AccessArticle

Termite Resistance of MDF Panels Treated with Various Boron Compounds

by Mustafa Usta, Derya Ustaomer, Saip Nami Kartal and Sedat Ondaral

Int. J. Mol. Sci. 2009, 10(6), 2789-2797; https://doi.org/10.3390/ijms10062789 - 19 Jun 2009

Cited by 12 | Viewed by 11410

Abstract

In this study, the effects of various boron compounds on the termite resistance of MDF panels were evaluated. Either borax (BX), boric acid (BA), zinc borate (ZB), or sodium perborate tetrahydrate (SPT) were added to urea-formaldehyde (UF) resin at target contents of 1%, [...] Read more.

In this study, the effects of various boron compounds on the termite resistance of MDF panels were evaluated. Either borax (BX), boric acid (BA), zinc borate (ZB), or sodium perborate tetrahydrate (SPT) were added to urea-formaldehyde (UF) resin at target contents of 1%, 1.5%, 2% and 2.5% based on dry fiber weight. The panels were then manufactured using 12% urea-formaldehyde resin and 1% NH₄Cl. MDF samples from the panels were tested against the subterranean termites, Coptotermes formosanus Shiraki. Laboratory termite resistance tests showed that all samples containing boron compounds had greater resistance against termite attack compared to untreated MDF samples. At the second and third weeks of exposure, nearly 100% termite mortalities were recorded in all boron compound treated samples. The highest termite mortalities were determined in the samples with either BA or BX. Also, it was found that SPT showed notable performance on the termite mortality. As chemical loadings increased, termite mortalities increased, and at the same time the weight losses of the samples decreased. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Yeast Two-Hybrid, a Powerful Tool for Systems Biology

by Anna Brückner, Cécile Polge, Nicolas Lentze, Daniel Auerbach and Uwe Schlattner

Int. J. Mol. Sci. 2009, 10(6), 2763-2788; https://doi.org/10.3390/ijms10062763 - 18 Jun 2009

Cited by 382 | Viewed by 45257

Abstract

A key property of complex biological systems is the presence of interaction networks formed by its different components, primarily proteins. These are crucial for all levels of cellular function, including architecture, metabolism and signalling, as well as the availability of cellular energy. Very [...] Read more.

A key property of complex biological systems is the presence of interaction networks formed by its different components, primarily proteins. These are crucial for all levels of cellular function, including architecture, metabolism and signalling, as well as the availability of cellular energy. Very stable, but also rather transient and dynamic protein-protein interactions generate new system properties at the level of multiprotein complexes, cellular compartments or the entire cell. Thus, interactomics is expected to largely contribute to emerging fields like systems biology or systems bioenergetics. The more recent technological development of high-throughput methods for interactomics research will dramatically increase our knowledge of protein interaction networks. The two most frequently used methods are yeast two-hybrid (Y2H) screening, a well established genetic in vivo approach, and affinity purification of complexes followed by mass spectrometry analysis, an emerging biochemical in vitro technique. So far, a majority of published interactions have been detected using an Y2H screen. However, with the massive application of this method, also some limitations have become apparent. This review provides an overview on available yeast two-hybrid methods, in particular focusing on more recent approaches. These allow detection of protein interactions in their native environment, as e.g. in the cytosol or bound to a membrane, by using cytosolic signalling cascades or split protein constructs. Strengths and weaknesses of these genetic methods are discussed and some guidelines for verification of detected protein-protein interactions are provided. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics)

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Open AccessArticle

Titration Calorimetry Standards and the Precision of Isothermal Titration Calorimetry Data

by Lina Baranauskienė, Vilma Petrikaitė, Jurgita Matulienė and Daumantas Matulis

Int. J. Mol. Sci. 2009, 10(6), 2752-2762; https://doi.org/10.3390/ijms10062752 - 18 Jun 2009

Cited by 78 | Viewed by 16020

Abstract

Current Isothermal Titration Calorimetry (ITC) data in the literature have relatively high errors in the measured enthalpies of protein-ligand binding reactions. There is a need for universal validation standards for titration calorimeters. Several inorganic salt co-precipitation and buffer protonation reactions have been suggested [...] Read more.

Current Isothermal Titration Calorimetry (ITC) data in the literature have relatively high errors in the measured enthalpies of protein-ligand binding reactions. There is a need for universal validation standards for titration calorimeters. Several inorganic salt co-precipitation and buffer protonation reactions have been suggested as possible enthalpy standards. The performances of several commercial calorimeters, including the VP-ITC, ITC200, and Nano ITC-III, were validated using these suggested standard reactions. Full article

(This article belongs to the Special Issue Isothermal Titration Calorimetry)

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Open AccessArticle

Variation in Dehydration Tolerance, ABA Sensitivity and Related Gene Expression Patterns in D-Genome Progenitor and Synthetic Hexaploid Wheat Lines

by Yumeto Kurahashi, Akihiro Terashima and Shigeo Takumi

Int. J. Mol. Sci. 2009, 10(6), 2733-2751; https://doi.org/10.3390/ijms10062733 - 18 Jun 2009

Cited by 39 | Viewed by 14024

Abstract

The wild wheat Aegilops tauschii Coss. has extensive natural variation available for breeding of common wheat. Drought stress tolerance is closely related to abscisic acid (ABA) sensitivity. In this study, 17 synthetic hexaploid wheat lines, produced by crossing the tetraploid wheat cultivar Langdon [...] Read more.

The wild wheat Aegilops tauschii Coss. has extensive natural variation available for breeding of common wheat. Drought stress tolerance is closely related to abscisic acid (ABA) sensitivity. In this study, 17 synthetic hexaploid wheat lines, produced by crossing the tetraploid wheat cultivar Langdon with 17 accessions of Ae. tauschii, were used for comparative analysis of natural variation in drought tolerance and ABA sensitivity. Ae. tauschii showed wide natural variation, with weak association between the traits. Drought-sensitive accessions of Ae. tauschii exhibited significantly less ABA sensitivity. D-genome variations observed at the diploid genome level were not necessarily reflected in synthetic wheats. However, synthetic wheats derived from the parental Ae. tauschii accessions with high drought tolerance were significantly more tolerant to drought stress than those from drought-sensitive accessions. Moreover, synthetic wheats with high drought tolerance showed significantly higher ABA sensitivity than drought-sensitive synthetic lines. In the hexaploid genetic background, therefore, weak association of ABA sensitivity with drought tolerance wasobserved. To study differences in gene expression patterns between stress-tolerant and -sensitive lines, levels of two Cor/Lea and three transcription factor gene transcripts were compared. The more tolerant accession of Ae. tauschii tended to accumulate more abundant transcripts of the examined genes than the sensitive accession under stress conditions. The expression patterns in the synthetic wheats seemed to be additive for parental lines exposed to drought and ABA treatments. However, the transcript levels of transcription factor genes in the synthetic wheats did not necessarily correspond to the postulated levels based on expression in parental lines. Allopolyploidization altered the expression levels of the stress-responsive genes in synthetic wheats. Full article

(This article belongs to the Special Issue Biotic and Abiotic Stress)

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Open AccessArticle

Amino Acid Synthesis in a Supercritical Carbon Dioxide - Water System

by Kouki Fujioka, Yasuhiro Futamura, Tomoo Shiohara, Akiyoshi Hoshino, Fumihide Kanaya, Yoshinobu Manome and Kenji Yamamoto

Int. J. Mol. Sci. 2009, 10(6), 2722-2732; https://doi.org/10.3390/ijms10062722 - 15 Jun 2009

Cited by 6 | Viewed by 13002

Abstract

Mars is a CO₂-abundant planet, whereas early Earth is thought to be also CO₂-abundant. In addition, water was also discovered on Mars in 2008. From the facts and theory, we assumed that soda fountains were present on both planets, [...] Read more.

Mars is a CO₂-abundant planet, whereas early Earth is thought to be also CO₂-abundant. In addition, water was also discovered on Mars in 2008. From the facts and theory, we assumed that soda fountains were present on both planets, and this affected amino acid synthesis. Here, using a supercritical CO₂/liquid H₂O (10:1) system which mimicked crust soda fountains, we demonstrate production of amino acids from hydroxylamine (nitrogen source) and keto acids (oxylic acid sources). In this research, several amino acids were detected with an amino acid analyzer. Moreover, alanine polymers were detected with LC-MS. Our research lights up a new pathway in the study of life’s origin. Full article

(This article belongs to the Special Issue Origin of Life)

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Open AccessReview

Precambrian Lunar Volcanic Protolife

by Jack Green

Int. J. Mol. Sci. 2009, 10(6), 2681-2721; https://doi.org/10.3390/ijms10062681 - 11 Jun 2009

Cited by 2 | Viewed by 13210

Abstract

Five representative terrestrial analogs of lunar craters are detailed relevant to Precambrian fumarolic activity. Fumarolic fluids contain the ingredients for protolife. Energy sources to derive formaldehyde, amino acids and related compounds could be by flow charging, charge separation and volcanic shock. With no [...] Read more.

Five representative terrestrial analogs of lunar craters are detailed relevant to Precambrian fumarolic activity. Fumarolic fluids contain the ingredients for protolife. Energy sources to derive formaldehyde, amino acids and related compounds could be by flow charging, charge separation and volcanic shock. With no photodecomposition in shadow, most fumarolic fluids at 40 K would persist over geologically long time periods. Relatively abundant tungsten would permit creation of critical enzymes, Fischer-Tropsch reactions could form polycyclic aromatic hydrocarbons and soluble volcanic polyphosphates would enable assembly of nucleic acids. Fumarolic stimuli factors are described. Orbital and lander sensors specific to protolife exploration including combined Raman/laser-induced breakdown spectrocsopy are evaluated. Full article

(This article belongs to the Special Issue Origin of Life)

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Open AccessArticle

Measurement of Nanomolar Dissociation Constants by Titration Calorimetry and Thermal Shift Assay – Radicicol Binding to Hsp90 and Ethoxzolamide Binding to CAII

by Asta Zubrienė, Jurgita Matulienė, Lina Baranauskienė, Jelena Jachno, Jolanta Torresan, Vilma Michailovienė, Piotras Cimmperman and Daumantas Matulis

Int. J. Mol. Sci. 2009, 10(6), 2662-2680; https://doi.org/10.3390/ijms10062662 - 10 Jun 2009

Cited by 51 | Viewed by 14740

Abstract

The analysis of tight protein-ligand binding reactions by isothermal titration calorimetry (ITC) and thermal shift assay (TSA) is presented. The binding of radicicol to the N-terminal domain of human heat shock protein 90 (Hsp90aN) and the binding of ethoxzolamide to human carbonic [...] Read more.

The analysis of tight protein-ligand binding reactions by isothermal titration calorimetry (ITC) and thermal shift assay (TSA) is presented. The binding of radicicol to the N-terminal domain of human heat shock protein 90 (Hsp90aN) and the binding of ethoxzolamide to human carbonic anhydrase (hCAII) were too strong to be measured accurately by direct ITC titration and therefore were measured by displacement ITC and by observing the temperature-denaturation transitions of ligand-free and ligand-bound protein. Stabilization of both proteins by their ligands was profound, increasing the melting temperature by more than 10 ºC, depending on ligand concentration. Analysis of the melting temperature dependence on the protein and ligand concentrations yielded dissociation constants equal to 1 nM and 2 nM for Hsp90aN-radicicol and hCAII-ethoxzolamide, respectively. The ligand-free and ligand-bound protein fractions melt separately, and two melting transitions are observed. This phenomenon is especially pronounced when the ligand concentration is equal to about half the protein concentration. The analysis compares ITC and TSA data, accounts for two transitions and yields the ligand binding constant and the parameters of protein stability, including the Gibbs free energy and the enthalpy of unfolding. Full article

(This article belongs to the Special Issue Isothermal Titration Calorimetry)

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Open AccessReview

Periodic Density Functional Theory Investigation of the Uranyl Ion Sorption on Three Mineral Surfaces: A Comparative Study

by Jérôme Roques, Edouard Veilly and Eric Simoni

Int. J. Mol. Sci. 2009, 10(6), 2633-2661; https://doi.org/10.3390/ijms10062633 - 4 Jun 2009

Cited by 32 | Viewed by 21151

Abstract

Canister integrity and radionuclides retention is of prime importance for assessing the long term safety of nuclear waste stored in engineered geologic depositories. A comparative investigation of the interaction of uranyl ion with three different mineral surfaces has thus been undertaken in order [...] Read more.

Canister integrity and radionuclides retention is of prime importance for assessing the long term safety of nuclear waste stored in engineered geologic depositories. A comparative investigation of the interaction of uranyl ion with three different mineral surfaces has thus been undertaken in order to point out the influence of surface composition on the adsorption mechanism(s). Periodic DFT calculations using plane waves basis sets with the GGA formalism were performed on the TiO₂(110), Al(OH)₃(001) and Ni(111) surfaces. This study has clearly shown that three parameters play an important role in the uranyl adsorption mechanism: the solvent (H₂O) distribution at the interface, the nature of the adsorption site and finally, the surface atoms’ protonation state. Full article

(This article belongs to the Special Issue Application of Density Functional Theory)

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129 KiB

Open AccessReview

The Eukaryotic Cell Originated in the Integration and Redistribution of Hyperstructures from Communities of Prokaryotic Cells Based on Molecular Complementarity

by Vic Norris and Robert Root-Bernstein

Int. J. Mol. Sci. 2009, 10(6), 2611-2632; https://doi.org/10.3390/ijms10062611 - 4 Jun 2009

Cited by 12 | Viewed by 12105

Abstract

In the “ecosystems-first” approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the [...] Read more.

In the “ecosystems-first” approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions. Full article

(This article belongs to the Special Issue Origin of Life)

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Open AccessReview

Application of Ionic Liquids in High Performance Reversed-Phase Chromatography

by Ye Wang, Minglei Tian, Wentao Bi and Kyung Ho Row

Int. J. Mol. Sci. 2009, 10(6), 2591-2610; https://doi.org/10.3390/ijms10062591 - 4 Jun 2009

Cited by 92 | Viewed by 14506

Abstract

Ionic liquids, considered “green” chemicals, are widely used in many areas of analytical chemistry due to their unique properties. Recently, ionic liquids have been used as a kind of novel additive in separation and combined with silica to synthesize new stationary phase as [...] Read more.

Ionic liquids, considered “green” chemicals, are widely used in many areas of analytical chemistry due to their unique properties. Recently, ionic liquids have been used as a kind of novel additive in separation and combined with silica to synthesize new stationary phase as separation media. This review will focus on the properties and mechanisms of ionic liquids and their potential applications as mobile phase modifier and surface-bonded stationary phase in reversed-phase high performance liquid chromatography (RP-HPLC). Ionic liquids demonstrate advantages and potential in chromatographic field. Full article

(This article belongs to the Section Green Chemistry)

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Open AccessArticle

Tryptophanase-Catalyzed L-Tryptophan Synthesis from D-Serine in the Presence of Diammonium Hydrogen Phosphate

by Akihiko Shimada, Haruka Ozaki, Takeshi Saito and Fujii Noriko

Int. J. Mol. Sci. 2009, 10(6), 2578-2590; https://doi.org/10.3390/ijms10062578 - 3 Jun 2009

Cited by 12 | Viewed by 11961

Abstract

Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of L-tryptophan from L-serine and indole through a β-substitution mechanism of the ping-pong type, and has no activity on D-serine. We previously reported that tryptophanase changed its stereospecificity to [...] Read more.

Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of L-tryptophan from L-serine and indole through a β-substitution mechanism of the ping-pong type, and has no activity on D-serine. We previously reported that tryptophanase changed its stereospecificity to degrade D-tryptophan in highly concentrated diammonium hydrogen phosphate, (NH₄)₂HPO₄ solution. The present study provided the same stereospecific change seen in the D-tryptophan degradation reaction also occurs in tryptophan synthesis from D-serine. Tryptophanase became active to D-serine to synthesize L-tryptophan in the presence of diammonium hydrogen phosphate. This reaction has never been reported before. D-serine seems to undergo β-replacement via an enzyme-bonded α-aminoacylate intermediate to yield L-tryptophan. Full article

(This article belongs to the Special Issue Origin of Life)

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Open AccessReview

QSPR Studies on Aqueous Solubilities of Drug-Like Compounds

by Pablo R. Duchowicz and Eduardo A. Castro

Int. J. Mol. Sci. 2009, 10(6), 2558-2577; https://doi.org/10.3390/ijms10062558 - 3 Jun 2009

Cited by 53 | Viewed by 14783

Abstract

A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous [...] Read more.

A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and “screenability” of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic. Full article

(This article belongs to the Special Issue Recent Advances in QSAR/QSPR Theory)

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Open AccessReview

Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders

by Yahya E. Choonara, Viness Pillay, Lisa C. Du Toit, Girish Modi, Dinesh Naidoo, Valence M.K. Ndesendo and Sibongile R. Sibambo

Int. J. Mol. Sci. 2009, 10(6), 2510-2557; https://doi.org/10.3390/ijms10062510 - 3 Jun 2009

Cited by 67 | Viewed by 20055

Abstract

The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order [...] Read more.

The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Huntington’s disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders’ in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions. Full article

(This article belongs to the Special Issue Advances in Molecular Neuropathology)

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Open AccessArticle

Purification, Crystallization and Preliminary X-ray Crystallographic Studies of RAIDD Death-Domain (DD)

by Tae-ho Jang and Hyun Ho Park

Int. J. Mol. Sci. 2009, 10(6), 2501-2509; https://doi.org/10.3390/ijms10062501 - 3 Jun 2009

Cited by 8 | Viewed by 10601

Abstract

Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions with [...] Read more.

Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions with Caspase-2 and PIDD through CARD and DD respectively and formation of PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into pET26b vector was expressed in E. coli cells and purified by nickel affinity chromatography and gel filtration. Although it has been known that the most DDs are not soluble in physiological condition, RAIDD DD was soluble and interacts tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has been crystallized. Crystals are trigonal and belong to space group P3₁21 (or its enantiomorph P3₂21) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 Å and γ = 120°. The crystals were obtained at room temperature and diffracted to 2.0 Å resolution. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

by Lu Cheng, Qinyu Ge, Pengfeng Xiao, Beili Sun, Xiaoyan Ke, Yunfei Bai and Zuhong Lu

Int. J. Mol. Sci. 2009, 10(6), 2487-2500; https://doi.org/10.3390/ijms10062487 - 2 Jun 2009

Cited by 22 | Viewed by 17482

Abstract

Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined [...] Read more.

Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ² = 7.809, p = 0.005) and genotype (χ² = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ² = 28.19，p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples. Full article

(This article belongs to the Section Biochemistry)

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268 KiB

Open AccessArticle

Voltage-Dependent Anion Channel 2 of Arabidopsis thaliana (AtVDAC2) Is Involved in ABA-Mediated Early Seedling Development

by Jinping Yan, Han He, Shibo Tong, Wanrong Zhang, Jianmei Wang, Xufeng Li and Yi Yang

Int. J. Mol. Sci. 2009, 10(6), 2476-2486; https://doi.org/10.3390/ijms10062476 - 26 May 2009

Cited by 27 | Viewed by 14291

Abstract

The voltage-dependent anion channel (VDAC) is the major transport protein in the outer membrane of mitochondria and plays crucial roles in energy metabolism, apoptosis, and metabolites transport. In plants, the expression of VDACs can be affected by different stresses, including drought, salinity and [...] Read more.

The voltage-dependent anion channel (VDAC) is the major transport protein in the outer membrane of mitochondria and plays crucial roles in energy metabolism, apoptosis, and metabolites transport. In plants, the expression of VDACs can be affected by different stresses, including drought, salinity and pathogen defense. In this study, we investigated the expression pattern of AtVDAC2 in A. thaliana and found ABA suppressed the accumulation of AtVDAC2 transcripts. Further, phenotype analysis of this VDAC deregulated-expression transgenic Arabidopsis plants indicated that AtVDAC2 anti-sense line showed an ABA-insensitivity phenotype during the early seedling development under ABA treatment. The results suggested that AtVDAC2 might be involved in ABA signaling in A. thaliana. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

An Updated Review of Tyrosinase Inhibitors

by Te-Sheng Chang

Int. J. Mol. Sci. 2009, 10(6), 2440-2475; https://doi.org/10.3390/ijms10062440 - 26 May 2009

Cited by 1268 | Viewed by 65520

Abstract

Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are [...] Read more.

Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed. Full article

(This article belongs to the Special Issue Inhibitors of Melanogenesis Related Processes: Application to Food and Cosmetic Industry)

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Int. J. Mol. Sci., Volume 10, Issue 6 (June 2009) – 22 articles , Pages 2440-2872

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