scholarly journals ABCG5/G8: a structural view to pathophysiology of the hepatobiliary cholesterol secretion

2019 ◽  
Vol 47 (5) ◽  
pp. 1259-1268 ◽  
Author(s):  
Aiman A. Zein ◽  
Rupinder Kaur ◽  
Toka O.K. Hussein ◽  
Gregory A. Graf ◽  
Jyh-Yeuan Lee
Keyword(s):  
Structural Information ◽  
Genetic Disorder ◽  
Structural Features ◽  
Sterol Transport ◽  
Cholesterol Excretion ◽  
Function Relationship ◽  
Cholesterol Secretion ◽  
First Time ◽  
Mechanistic View ◽  
Inactivating Mutations

Abstract The ABCG5/G8 heterodimer is the primary neutral sterol transporter in hepatobiliary and transintestinal cholesterol excretion. Inactivating mutations on either the ABCG5 or ABCG8 subunit cause Sitosterolemia, a rare genetic disorder. In 2016, a crystal structure of human ABCG5/G8 in an apo state showed the first structural information on ATP-binding cassette (ABC) sterol transporters and revealed several structural features that were observed for the first time. Over the past decade, several missense variants of ABCG5/G8 have been associated with non-Sitosterolemia lipid phenotypes. In this review, we summarize recent pathophysiological and structural findings of ABCG5/G8, interpret the structure-function relationship in disease-causing variants and describe the available evidence that allows us to build a mechanistic view of ABCG5/G8-mediated sterol transport.

ASSOCIATION OF FEATURE GENE EXPRESSION WITH STRUCTURAL FINGERPRINTS OF CHEMICAL COMPOUNDS

2011 ◽  
Vol 09 (04) ◽  
pp. 503-519 ◽  
Author(s):  
YUN LI ◽  
KANG TU ◽  
SIYUAN ZHENG ◽  
JINGFANG WANG ◽  
YIXUE LI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Structural Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Structural Difference ◽  
Structural Features ◽  
Molecular Structures ◽  
Transcriptomics Data ◽  
Function Relationship ◽  
Relationship Of

Exploring the relationship between a chemical structure and its biological function is of great importance for drug discovery. For understanding the mechanisms of drug action, researchers traditionally focused on the molecular structures in the context of interactions with targets. The newly emerged high-throughput "omics" technology opened a new dimension to study the structure–function relationship of chemicals. Previous studies made attempts to introduce transcriptomics data into chemical function investigation. But little effort has been made to link structural fingerprints of compounds with defined intracellular functions, i.e. expression of particular genes and altered pathways. By integrating the chemical structural information with the gene expression profiles of chemical-treated cells, we developed a novel method to associate the structural difference between compounds with the expression of a definite set of genes, which were called feature genes. A subtraction protocol was designed to extract a minimum gene set related to chemical structural features, which can be utilized in practice as markers for drug screening. Case studies demonstrated that our approach is capable of finding feature genes associated with chemical structural fingerprints.

Measurement and Reduction of Radiation Damage in Frozen Hydrated Crystalline Specimens

1978 ◽  
Vol 36 (3) ◽  
pp. 70-77 ◽  
Author(s):  
R.M. Glaeser ◽  
S.B. Hayward
Keyword(s):  
Diffraction Pattern ◽  
Structural Information ◽  
Structural Disorder ◽  
Structural Features ◽  
Biological Macromolecules ◽  
Diffraction Intensity ◽  
Object Structure ◽  
Specimen Material ◽  
Unit Cells ◽  
Identical Unit

Highly ordered or crystalline biological macromolecules become severely damaged and structurally disordered after a brief electron exposure. Evidence that damage and structural disorder are occurring is clearly given by the fading and eventual disappearance of the specimen's electron diffraction pattern. The fading and disappearance of sharp diffraction spots implies a corresponding disappearance of periodic structural features in the specimen. By the same token, there is a oneto- one correspondence between the disappearance of the crystalline diffraction pattern and the disappearance of reproducible structural information that can be observed in the images of identical unit cells of the object structure. The electron exposures that result in a significant decrease in the diffraction intensity will depend somewhat upon the resolution (Bragg spacing) involved, and can vary considerably with the chemical makeup and composition of the specimen material.

HAZARD: An Expert System for Risk Assessment of Environmental Chemicals

1987 ◽  
Vol 26 (01) ◽  
pp. 13-23 ◽  
Author(s):  
H. W. Gottinger
Keyword(s):  
Expert System ◽  
Structural Information ◽  
Chemical Carcinogenesis ◽  
Structural Features ◽  
Environmental Chemicals ◽  
Chemical Carcinogens ◽  
Carcinogenic Activity ◽  
Current State ◽  
Structure Activity ◽  
Carcinogenic Potential

AbstractThe purpose of this paper is to report on an expert system in design that screens for potential hazards from environmental chemicals on the basis of structure-activity relationships in the study of chemical carcinogenesis, particularly with respect to analyzing the current state of known structural information about chemical carcinogens and predicting the possible carcinogenicity of untested chemicals. The structure-activity tree serves as an index of known chemical structure features associated with carcinogenic activity. The basic units of the tree are the principal recognized classes of chemical carcinogens that are subdivided into subclasses known as nodes according to specific structural features that may reflect differences in carcinogenic potential among chemicals in the class. An analysis of a computerized data base of known carcinogens (knowledge base) is proposed using the structure-activity tree in order to test the validity of the tree as a classification scheme (inference engine).

Rapid Online Buffer Exchange: A Method for Screening of Proteins, Protein Complexes, and Cell Lysates by Native Mass Spectrometry

2019 ◽  
Author(s):  
Zachary VanAernum ◽  
Florian Busch ◽  
Benjamin J. Jones ◽  
Mengxuan Jia ◽  
Zibo Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Speed ◽  
Structural Information ◽  
Protein Complexes ◽  
High Sensitivity ◽  
Native Mass Spectrometry ◽  
Structural Features ◽  
Consumer Products ◽  
Cell Lysates ◽  
Protein Expression And Purification

It is important to assess the identity and purity of proteins and protein complexes during and after protein purification to ensure that samples are of sufficient quality for further biochemical and structural characterization, as well as for use in consumer products, chemical processes, and therapeutics. Native mass spectrometry (nMS) has become an important tool in protein analysis due to its ability to retain non-covalent interactions during measurements, making it possible to obtain protein structural information with high sensitivity and at high speed. Interferences from the presence of non-volatiles are typically alleviated by offline buffer exchange, which is timeconsuming and difficult to automate. We provide a protocol for rapid online buffer exchange (OBE) nMS to directly screen structural features of pre-purified proteins, protein complexes, or clarified cell lysates. Information obtained by OBE nMS can be used for fast (<5 min) quality control and can further guide protein expression and purification optimization.

Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications

2020 ◽  
Vol 27 (37) ◽  
pp. 6306-6355 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Modular Architecture ◽  
Post Translational Modifications ◽  
Interaction Domains

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

A Systematic Review on Popularity, Application and Characteristics of Protein Secondary Structure Prediction Tools

2019 ◽  
Vol 16 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Elaheh Kashani-Amin ◽  
Ozra Tabatabaei-Malazy ◽  
Amirhossein Sakhteman ◽  
Bagher Larijani ◽  
Azadeh Ebrahim-Habibi
Keyword(s):  
Systematic Review ◽  
Secondary Structure ◽  
Structure Prediction ◽  
Web Of Science ◽  
Secondary Structure Prediction ◽  
Structural Information ◽  
Protein Secondary Structure ◽  
Structural Features ◽  
Prediction Tools ◽  
Insight Into

Background: Prediction of proteins’ secondary structure is one of the major steps in the generation of homology models. These models provide structural information which is used to design suitable ligands for potential medicinal targets. However, selecting a proper tool between multiple Secondary Structure Prediction (SSP) options is challenging. The current study is an insight into currently favored methods and tools, within various contexts. Objective: A systematic review was performed for a comprehensive access to recent (2013-2016) studies which used or recommended protein SSP tools. Methods: Three databases, Web of Science, PubMed and Scopus were systematically searched and 99 out of the 209 studies were finally found eligible to extract data. Results: Four categories of applications for 59 retrieved SSP tools were: (I) prediction of structural features of a given sequence, (II) evaluation of a method, (III) providing input for a new SSP method and (IV) integrating an SSP tool as a component for a program. PSIPRED was found to be the most popular tool in all four categories. JPred and tools utilizing PHD (Profile network from HeiDelberg) method occupied second and third places of popularity in categories I and II. JPred was only found in the two first categories, while PHD was present in three fields. Conclusion: This study provides a comprehensive insight into the recent usage of SSP tools which could be helpful for selecting a proper tool.

scholarly journals Computational Modeling to Explain Why 5,5-Diarylpentadienamides are TRPV1 Antagonists

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1765
Author(s):  
Julio Caballero
Keyword(s):  
Transient Receptor Potential ◽  
Structural Information ◽  
Chemical Activation ◽  
Receptor Potential ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Residues ◽  
Topological Features ◽  
Transient Receptor

Several years ago, the crystallographic structures of the transient receptor potential vanilloid 1 (TRPV1) in the presence of agonists and antagonists were reported, providing structural information about its chemical activation and inactivation. TRPV1’s activation increases the transport of calcium and sodium ions, leading to the excitation of sensory neurons and the perception of pain. On the other hand, its antagonistic inactivation has been explored to design analgesic drugs. The interactions between the antagonists 5,5-diarylpentadienamides (DPDAs) and TRPV1 were studied here to explain why they inactivate TRPV1. The present work identified the structural features of TRPV1–DPDA complexes, starting with a consideration of the orientations of the ligands inside the TRPV1 binding site by using molecular docking. After this, a chemometrics analysis was performed (i) to compare the orientations of the antagonists (by using LigRMSD), (ii) to describe the recurrent interactions between the protein residues and ligand groups in the complexes (by using interaction fingerprints), and (iii) to describe the relationship between topological features of the ligands and their differential antagonistic activities (by using a quantitative structure–activity relationship (QSAR) with 2D autocorrelation descriptors). The interactions between the DPDA groups and the residues Y511, S512, T550, R557, and E570 (with a recognized role in the binding of classic ligands), and the occupancy of isoquinoline or 3-hydroxy-3,4-dihydroquinolin-2(1H)-one groups of the DPDAs in the vanilloid pocket of TRPV1 were clearly described. Based on the results, the structural features that explain why DPDAs inactivate TRPV1 were clearly exposed. These features can be considered for the design of novel TRPV1 antagonists.

Capsule endoscopy findings in congenital afibrinogenemia-associated angiopathy

VASA ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 383-385 ◽  
Author(s):  
Katsinelos ◽  
Vasiliadis ◽  
Soufleris ◽  
Chatzimavroudis ◽  
Zavos ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Capsule Endoscopy ◽  
Intestinal Ischemia ◽  
Genetic Disorder ◽  
Rare Genetic Disorder ◽  
Unusual Condition ◽  
Congenital Afibrinogenemia ◽  
Abdominal Arteries ◽  
First Time

Congenital afibrinogenemia is a rare genetic disorder characterized by the complete absence of functional fibrinogen. We report a 22-year-old female who developed nephrogenic arterial hypertension and intestinal ischemia due to congenital afibrinogenemia-associated angiopathy of large abdominal arteries. We describe, for the first time, the capsule findings and discuss the pathophysiology of this unusual condition.

How Crystals Form from a Cloud of Atoms

2011 ◽  
Vol 675-677 ◽  
pp. 3-7
Author(s):  
Peter Häussler ◽  
Martin Stiehler
Keyword(s):  
Structure Formation ◽  
Fundamental Equation ◽  
Structural Features ◽  
Local Order ◽  
Total System ◽  
Angular Momenta ◽  
General Dynamics ◽  
Bloch’S Theorem ◽  
The Given ◽  
First Time

Structure formation, the condensation of a cloud of atoms to a crystal is still not well understood. Disordered sytems (amorphous/liquid) should be in the center of this research, they are the precursors of any crystal. We consider elementary systems, as well as binary, or ternary amorphous alloys, irrespective whether they are metallically, covalently or ionically bonded and describe the process of structure formation in the formal language of thermodynamics but, as far as we know for the first time, by an extended version (general dynamics), based on the complete Gibbs fundamental equation, applied to internal subsystems. Major structural features evolve from global resonances between formerly independent internal subsystems by exchanging momenta and angular momenta, both accompanied by energy. By this they adjust mutually their internal features and create spherical-periodic structural order at medium-range distances. Under the given external constraints the resonances get optimized by selforganization. Global resonances of the type considered have clearly to be distinguished from local resonances between individual ions (described by quantum chemistry) forming local order. The global resonances cause anti-bonding (non-equilibrium) as well as bonding (equilibrium) states of the coupled total system, occupying the latter to form new structurally extended order. The transition to equilibrium creates entropy which itself leaves the system together with energy. At resonance the energetical splitting between the bonding and anti-bonding state is largest, the creation of entropy and the decrease of the total energy therefore, too. The crystal, finally, evolves by additionally optimizing a resonance based on angular momentum, and the additional adjustments of the local resonances to the global ones, theoretically done by applying Bloch’s theorem.

scholarly journals Earthquake-induced debris flows at Popocatépetl Volcano, Mexico

2020 ◽  
Author(s):  
Velio Coviello ◽  
Lucia Capra ◽  
Gianluca Norini ◽  
Norma Dávila ◽  
Dolores Ferrés ◽  
...  
Keyword(s):  
Debris Flows ◽  
Horizontal Stress ◽  
Structural Features ◽  
Volcanic Edifice ◽  
Western Slope ◽  
Slope Failures ◽  
Ground Shaking ◽  
Seismic Records ◽  
Maximum Horizontal Stress ◽  
First Time

Abstract. The M7.1 Puebla-Morelos earthquake that occurred on 19 September 2017, with epicenter located ∼ 70 km SW from Popocatépetl volcano, severely hit central Mexico. Seismic shaking of the volcanic edifice induced by the earthquake triggered hundreds of shallow landslides on the volcanic flanks, remobilizing loose pyroclastic deposits and saturated soils. The largest landslides occurred on the slopes of aligned ENE-WSW-trending ravines on opposite sides of the volcanic cone, roughly parallel to the regional maximum horizontal stress and local volcanotectonic structural features. This configuration may suggest transient reactivation of local faults and extensional fractures as one of the mechanisms that has weakened the volcanic edifice and promoted the largest slope failures. The seismic records from a broadband station located at few kilometers from the main landslides are used to infer the intensity of ground shaking that triggered the slope failures. The material involved in the larger landslides, mainly ash and pumice fall deposits from late Holocene eruptions with a total volume of about 106 cubic meters, transformed into two large debris flows on the western slope of the volcano and one on its eastern side. The debris flows were highly viscous and contained abundant large woods (about 105 cubic meter). Their peculiar rheology is reconstructed by field evidences and analyzing the grain size distribution of samples from both landslide scars and deposits. This is the first time that such flows were observed at this volcano. Our work provides new insights to constrain a multi-hazard risk assessment for Popocatépetl and other continental active volcanoes.

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