scholarly journals GAG-DB, the New Interface of the Three-Dimensional Landscape of Glycosaminoglycans

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1660
Author(s):  
Serge Pérez ◽  
François Bonnardel ◽  
Frédérique Lisacek ◽  
Anne Imberty ◽  
Sylvie Ricard Blum ◽  
...  
Keyword(s):  
Quaternary Structure ◽  
Graphical Representation ◽  
Dermatan Sulfate ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Keratan Sulfate ◽  
Data Bank ◽  
Scattering Data ◽  
Gag Protein ◽  
X Ray

Glycosaminoglycans (GAGs) are complex linear polysaccharides. GAG-DB is a curated database that classifies the three-dimensional features of the six mammalian GAGs (chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate) and their oligosaccharides complexed with proteins. The entries are structures of GAG and GAG-protein complexes determined by X-ray single-crystal diffraction methods, X-ray fiber diffractometry, solution NMR spectroscopy, and scattering data often associated with molecular modeling. We designed the database architecture and the navigation tools to query the database with the Protein Data Bank (PDB), UniProtKB, and GlyTouCan (universal glycan repository) identifiers. Special attention was devoted to the description of the bound glycan ligands using simple graphical representation and numerical format for cross-referencing to other databases in glycoscience and functional data. GAG-DB provides detailed information on GAGs, their bound protein ligands, and features their interactions using several open access applications. Binding covers interactions between monosaccharides and protein monosaccharide units and the evaluation of quaternary structure. GAG-DB is freely available.

scholarly journals Glycosaminoglycan–Protein Interactions: The First Draft of the Glycosaminoglycan Interactome

2020 ◽  
pp. 002215542094640 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Olivier Clerc ◽  
Sylvie Ricard-Blum
Keyword(s):  
Extracellular Matrix ◽  
Protein Interactions ◽  
Dermatan Sulfate ◽  
Protein Complexes ◽  
Keratan Sulfate ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Matrix Proteins ◽  
Matrix Assembly ◽  
Gag Protein

The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. These interactions mediate their functions, from embryonic development to extracellular matrix assembly and regulation of cell signaling in various physiological and pathological contexts such as angiogenesis, cancer, neurodegenerative diseases, and infections. We give an overview of GAG–protein interactions (i.e., specificity and chemical features of GAG- and protein-binding sequences), and review the available GAG–protein interaction networks. We also provide the first comprehensive draft of the GAG interactome composed of 832 biomolecules (827 proteins and five GAGs) and 932 protein–GAG interactions. This network is a scaffold, which in the future should integrate structures of GAG–protein complexes, quantitative data of the abundance of GAGs in tissues to build tissue-specific interactomes, and GAG interactions with metal ions such as calcium, which plays a major role in the assembly of the extracellular matrix and its interactions with cells. This contextualized interactome will be useful to identify druggable GAG–protein interactions for therapeutic purpose:

Three-dimensional crystallization of membrane proteins

1988 ◽  
Vol 21 (4) ◽  
pp. 429-477 ◽  
Author(s):  
W. Kühlbrandt
Keyword(s):  
High Resolution ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Biological Macromolecules ◽  
X Ray ◽  
X Ray Crystallography ◽  
Membrane Protein Complexes ◽  
Essential Prerequisite

As recently as 10 years ago, the prospect of solving the structure of any membrane protein by X-ray crystallography seemed remote. Since then, the threedimensional (3-D) structures of two membrane protein complexes, the bacterial photosynthetic reaction centres of Rhodopseudomonas viridis (Deisenhofer et al. 1984, 1985) and of Rhodobacter sphaeroides (Allen et al. 1986, 1987 a, 6; Chang et al. 1986) have been determined at high resolution. This astonishing progress would not have been possible without the pioneering work of Michel and Garavito who first succeeded in growing 3-D crystals of the membrane proteins bacteriorhodopsin (Michel & Oesterhelt, 1980) and matrix porin (Garavito & Rosenbusch, 1980). X-ray crystallography is still the only routine method for determining the 3-D structures of biological macromolecules at high resolution and well-ordered 3-D crystals of sufficient size are the essential prerequisite.

ELLSTAT: shape modeling for solution small-angle scattering of proteins and protein complexes with automated statistical characterization

2006 ◽  
Vol 39 (5) ◽  
pp. 671-675 ◽  
Author(s):  
William T. Heller
Keyword(s):  
Small Angle ◽  
Protein Complexes ◽  
Structural Parameters ◽  
Shape Modeling ◽  
Scattering Data ◽  
Model Parameters ◽  
Data Sets ◽  
Statistical Characterization ◽  
X Ray ◽  
Angle Scattering

A method is presented for constructing one- and two-ellipsoid, core-shell-ellipsoid, cylinder and ellipsoid-plus-cylinder models from small-angle X-ray and neutron scattering data that calculates statistics on the resulting structural parameters. The method, implemented in the softwareELLSTAT, is capable of simultaneously fitting against several data sets and calculates averages, standard deviations and coefficients of linear correlation between the structural parameters of the resulting models. In this way, an improved understanding of the extent of the variability in and the interdependency between the model parameters that fit the input scattering data is developed, thereby providing a measure of the uniqueness of the models.

scholarly journals Merging single-shot XFEL diffraction data from inorganic nanoparticles: a new approach to size and orientation determination

IUCrJ ◽  
2017 ◽  
Vol 4 (6) ◽  
pp. 741-750 ◽  
Author(s):  
Xuanxuan Li ◽  
John C. H. Spence ◽  
Brenda G. Hogue ◽  
Haiguang Liu
Keyword(s):  
Short Pulse ◽  
Dimensional Space ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
Inorganic Nanoparticles ◽  
Scattering Data ◽  
Core Shell ◽  
Single Shot ◽  
X Ray ◽  
Data Merging

X-ray free-electron lasers (XFELs) provide new opportunities for structure determination of biomolecules, viruses and nanomaterials. With unprecedented peak brilliance and ultra-short pulse duration, XFELs can tolerate higher X-ray doses by exploiting the femtosecond-scale exposure time, and can thus go beyond the resolution limits achieved with conventional X-ray diffraction imaging techniques. Using XFELs, it is possible to collect scattering information from single particles at high resolution, however particle heterogeneity and unknown orientations complicate data merging in three-dimensional space. Using the Linac Coherent Light Source (LCLS), synthetic inorganic nanocrystals with a core–shell architecture were used as a model system for proof-of-principle coherent diffractive single-particle imaging experiments. To deal with the heterogeneity of the core–shell particles, new computational methods have been developed to extract the particle size and orientation from the scattering data to assist data merging. The size distribution agrees with that obtained by electron microscopy and the merged data support a model with a core–shell architecture.

scholarly journals Two practical Java software tools for small-angle X-ray scattering analysis of biomolecules

2014 ◽  
Vol 47 (2) ◽  
pp. 810-815 ◽  
Author(s):  
Andreas Hofmann ◽  
Andrew E. Whitten
Keyword(s):  
Small Angle ◽  
Three Dimensional ◽  
Small Angle Scattering ◽  
Ease Of Use ◽  
Scattering Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Angle Scattering ◽  
Three Dimensional Models ◽  
Ray Scattering

Small-angle X-ray scattering has established itself as a common technique in structural biology research. Here, two novel Java applications to aid modelling of three-dimensional macromolecular structures based on small-angle scattering data are described.MolScatis an application that computes small-angle scattering intensities from user-provided three-dimensional models. The program can fit the theoretical scattering intensities to experimental X-ray scattering data.SAFIRis a program for interactive rigid-body modelling into low-resolution shapes restored from small-angle scattering data. The program has been designed with an emphasis on ease of use and intuitive handling. An embedded version ofMolScatis used to enable quick evaluation of the fit between the model and experimental scattering data.SAFIRalso provides options to refine macromolecular complexes with optional user-specified restraints against scattering data by means of a Monte Carlo approach.

scholarly journals Mutation Sites Are Distant from Remdesivir Binding Site in Human SARS-CoV-2 RNA-Dependent RNA Polymerase

2021 ◽  
Author(s):  
Kunchur Guruprasad
Keyword(s):  
Protein Sequence ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Data Bank ◽  
Rna Dependent Rna Polymerase ◽  
Mutation Site ◽  
Cryo Electron Microscopy ◽  
Reference Protein ◽  
Beta Hairpin ◽  
Geographical Locations

<p>The comparison of 10,929 human SARS-CoV-2 RdRp protein sequences representing six geographical locations with the reference protein sequence in human SARS-CoV-2 genome isolate from Wuhan, China, identified 222 distinct mutation sites in the RdRp protein. The NiRAN and interface domains, Fingers, Palm and Thumb sub-domains were each associated with ~20% or more mutations compared to mutations in N-terminal, beta-hairpin or C-terminal regions of the protein. The Pro4715Leu mutation was predominantly observed in RdRp proteins from all six geographical locations; Africa, Asia, Europe, North America, Oceania and South America. None of the mutation site residues were within 3.2 Å interacting distance from remdesivir as observed in the three-dimensional cryo-electron microscopy structures of RdRp protein complexes available in the Protein Data Bank. Therefore, the mutations in human SARS-CoV-2 RdRp proteins, described in the present work, are not likely to cause resistance to remdesivir binding. Further, the mutations were also not associated with functionally important residues that would affect the enzyme’s function.</p>

A new algorithm for the reconstruction of protein molecular envelopes from X-ray solution scattering data

2019 ◽  
Vol 52 (5) ◽  
pp. 937-944
Author(s):  
John Badger
Keyword(s):  
Protein Structures ◽  
Three Dimensional ◽  
Protein Molecule ◽  
Scattering Data ◽  
Data Sets ◽  
Low Resolution ◽  
Jones Potential ◽  
X Ray ◽  
Pair Distance Distribution Function ◽  
Protein Shape

At sufficiently low resolution, the scattering density within the volume occupied by a well folded protein molecule appears relatively flat. By enforcing this condition, three-dimensional protein molecular envelopes may be reconstructed using information obtained from X-ray solution scattering profiles. A practical approach for solving the low-resolution structures of protein molecules from solution scattering data involves modelling the protein shape using a set of volume-filling points (`beads') and transforming the scattering data to a more convenient target, the pair distance distribution function, P(r). Using algorithms described here, the beads interact via a modified Lennard–Jones potential and their positions are adjusted and confined until they fit the expected protein volume and agreement with P(r) is obtained. This methodology allows the protein volume to be modelled by an arbitrary, user-defined number of beads, enabling the rapid reconstruction of protein structures of widely varying sizes. Tests carried out with a variety of synthetic and experimental data sets show that this approach gives efficient and reliable determinations of protein molecular envelopes.

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