scholarly journals Covering complete proteomes with X-ray structures: a current snapshot

2014 ◽  
Vol 70 (11) ◽  
pp. 2781-2793 ◽  
Author(s):  
Marcin J. Mizianty ◽  
Xiao Fan ◽  
Jing Yan ◽  
Eric Chalmers ◽  
Christopher Woloschuk ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Structure Determination ◽  
Large Scale ◽  
Structural Model ◽  
Target Selection ◽  
Three Dimensional ◽  
X Ray ◽  
X Ray Crystallography ◽  
Knowledge Based ◽  
Wide Range

Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtained through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.

scholarly journals Structure of catalase determined by MicroED

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Brent L Nannenga ◽  
Dan Shi ◽  
Johan Hattne ◽  
Francis E Reyes ◽  
Tamir Gonen
Keyword(s):  
Structure Determination ◽  
Three Dimensional ◽  
Bovine Liver ◽  
Electron Crystallography ◽  
X Ray ◽  
X Ray Crystallography ◽  
Continuous Rotation ◽  
Bovine Liver Catalase ◽  
Diffraction Patterns ◽  
Atomic Analysis

MicroED is a recently developed method that uses electron diffraction for structure determination from very small three-dimensional crystals of biological material. Previously we used a series of still diffraction patterns to determine the structure of lysozyme at 2.9 Å resolution with MicroED (<xref ref-type="bibr" rid="bib26">Shi et al., 2013</xref>). Here we present the structure of bovine liver catalase determined from a single crystal at 3.2 Å resolution by MicroED. The data were collected by continuous rotation of the sample under constant exposure and were processed and refined using standard programs for X-ray crystallography. The ability of MicroED to determine the structure of bovine liver catalase, a protein that has long resisted atomic analysis by traditional electron crystallography, demonstrates the potential of this method for structure determination.

Ulrich Wolfgang Arndt. 23 April 1924 — 24 March 2006

2014 ◽  
Vol 60 ◽  
pp. 39-55
Author(s):  
R. A. Crowther ◽  
A. G. W. Leslie
Keyword(s):  
Protein Structures ◽  
Three Dimensional ◽  
Direct Methods ◽  
Biological Molecules ◽  
Data Generation ◽  
Data Set ◽  
X Ray ◽  
X Ray Crystallography ◽  
Whole Process ◽  
Wide Range

Ulrich (Uli) Arndt was a physicist and engineer whose contributions to the development of a wide range of instrumentation for X-ray crystallography played an important part in our ability to solve the atomic structure of large biological molecules. Such detailed information about protein structures has for the past 50 years underpinned the huge advances in the field of molecular biology. His innovations spanned all aspects of data generation and collection, from improvements in X-ray tubes, through novel designs for diffractometers and cameras to film scanners and more direct methods of X-ray detection. When he started in the field, the intensities of individual X-ray reflections were often estimated by eye from films. By the end of his career the whole process of collecting from a crystal a three-dimensional data set, possibly comprising hundreds of thousands of measurements, was fully automated and very rapid.

scholarly journals 4-(4-Chlorophenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thione

Molbank ◽  
10.3390/m1047 ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. M1047 ◽  
Author(s):  
Chien Yeo ◽  
Ainnul Azizan ◽  
Edward Tiekink
Keyword(s):  
Hydrogen Bonds ◽  
Structure Determination ◽  
Title Compound ◽  
Uv Spectroscopy ◽  
Three Dimensional ◽  
Membered Ring ◽  
X Ray ◽  
X Ray Crystallography ◽  
Orthogonal Relationship ◽  
Ir And Uv Spectroscopy

The title compound, 4-(4-chlorophenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thione (1), was synthesized by a hetero-cyclization reaction of 4-chlorophenyl isothiocyanate and formic hydrazide. Compound 1 was characterized by a single-crystal X-ray structure determination as well as 1H and 13C{1H} NMR, IR, and UV spectroscopy, and microelemental analysis. X-ray crystallography on 1 confirms the molecule exists as the thione tautomer and shows the five-membered ring to be planar and to form a dihedral angle of 82.70(5)° with the appended chlorophenyl ring, indicating an almost orthogonal relationship. In the molecular packing, supramolecular dimers are formed via thioamide-N–H⋯S(thione) hydrogen bonds and these are connected by C=S⋯π(triazolyl) and C-Cl⋯π(triazolyl) interactions, leading to a three-dimensional architecture.

scholarly journals PROBABILISTIC ENSEMBLES FOR IMPROVED INFERENCE IN PROTEIN-STRUCTURE DETERMINATION

2012 ◽  
Vol 10 (01) ◽  
pp. 1240009 ◽  
Author(s):  
AMEET SONI ◽  
JUDE SHAVLIK
Keyword(s):  
Protein Structure ◽  
Structure Determination ◽  
Protein Structures ◽  
Three Dimensional ◽  
Protein Structure Determination ◽  
Complex Problem ◽  
Approximate Inference ◽  
X Ray ◽  
X Ray Crystallography ◽  
Inference Methods

Protein X-ray crystallography — the most popular method for determining protein structures — remains a laborious process requiring a great deal of manual crystallographer effort to interpret low-quality protein images. Automating this process is critical in creating a high-throughput protein-structure determination pipeline. Previously, our group developed ACMI, a probabilistic framework for producing protein-structure models from electron-density maps produced via X-ray crystallography. ACMI uses a Markov Random Field to model the three-dimensional (3D) location of each non-hydrogen atom in a protein. Calculating the best structure in this model is intractable, so ACMI uses approximate inference methods to estimate the optimal structure. While previous results have shown ACMI to be the state-of-the-art method on this task, its approximate inference algorithm remains computationally expensive and susceptible to errors. In this work, we develop Probabilistic Ensembles in ACMI (PEA), a framework for leveraging multiple, independent runs of approximate inference to produce estimates of protein structures. Our results show statistically significant improvements in the accuracy of inference resulting in more complete and accurate protein structures. In addition, PEA provides a general framework for advanced approximate inference methods in complex problem domains.

scholarly journals A suite of software for processing MicroED data of extremely small protein crystals

2014 ◽  
Vol 47 (3) ◽  
pp. 1140-1145 ◽  
Author(s):  
Matthew G. Iadanza ◽  
Tamir Gonen
Keyword(s):  
Structure Determination ◽  
Ad Hoc ◽  
Source Code ◽  
Three Dimensional ◽  
Molecular Replacement ◽  
X Ray ◽  
X Ray Crystallography ◽  
Software Packages ◽  
Transmission Electron ◽  
Standard Software

Electron diffraction of extremely small three-dimensional crystals (MicroED) allows for structure determination from crystals orders of magnitude smaller than those used for X-ray crystallography. MicroED patterns, which are collected in a transmission electron microscope, were initially not amenable to indexing and intensity extraction by standard software, which necessitated the development of a suite of programs for data processing. The MicroED suite was developed to accomplish the tasks of unit-cell determination, indexing, background subtraction, intensity measurement and merging, resulting in data that can be carried forward to molecular replacement and structure determination. Thisad hocsolution has been modified for more general use to provide a means for processing MicroED data until the technique can be fully implemented into existing crystallographic software packages. The suite is written in Python and the source code is available under a GNU General Public License.

Beyond X-rays: an overview of emerging structural biology methods

2021 ◽  
Author(s):  
Jason E. Schaffer ◽  
Vandna Kukshal ◽  
Justin J. Miller ◽  
Vivian Kitainda ◽  
Joseph M. Jez
Keyword(s):  
Structure Determination ◽  
De Novo ◽  
Three Dimensional ◽  
Atomic Scale ◽  
X Rays ◽  
Time Resolved ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Methods ◽  
Main Technique

Structural biologists rely on X-ray crystallography as the main technique for determining the three-dimensional structures of macromolecules; however, in recent years, new methods that go beyond X-ray-based technologies are broadening the selection of tools to understand molecular structure and function. Simultaneously, national facilities are developing programming tools and maintaining personnel to aid novice structural biologists in de novo structure determination. The combination of X-ray free electron lasers (XFELs) and serial femtosecond crystallography (SFX) now enable time-resolved structure determination that allows for capture of dynamic processes, such as reaction mechanism and conformational flexibility. XFEL and SFX, along with microcrystal electron diffraction (MicroED), help side-step the need for large crystals for structural studies. Moreover, advances in cryogenic electron microscopy (cryo-EM) as a tool for structure determination is revolutionizing how difficult to crystallize macromolecules and/or complexes can be visualized at the atomic scale. This review aims to provide a broad overview of these new methods and to guide readers to more in-depth literature of these methods.

scholarly journals Improving diffraction resolution using a new dehydration method

2016 ◽  
Vol 72 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Qingqiu Huang ◽  
Doletha M. E. Szebenyi
Keyword(s):  
Escherichia Coli ◽  
Structure Determination ◽  
Three Dimensional ◽  
Archaeoglobus Fulgidus ◽  
Dimensional Structure ◽  
High Quality ◽  
X Ray ◽  
Three Dimensional Structure ◽  
X Ray Crystallography ◽  
Dry Out

The production of high-quality crystals is one of the major obstacles in determining the three-dimensional structure of macromolecules by X-ray crystallography. It is fairly common that a visually well formed crystal diffracts poorly to a resolution that is too low to be suitable for structure determination. Dehydration has proven to be an effective post-crystallization treatment for improving crystal diffraction quality. Several dehydration methods have been developed, but no single one of them is suitable for all crystals. Here, a new convenient and effective dehydration method is reported that makes use of a dehydrating solution that will not dry out in air for several hours. Using this dehydration method, the resolution ofArchaeoglobus fulgidusCas5a crystals has been increased from 3.2 to 1.95 Å and the resolution ofEscherichia coliLptA crystals has been increased from <5 to 3.4 Å.

scholarly journals HOMOLOGY MODELING OF SUBCUTANEOUS FILARIASIS DHFR PROTEINS

2017 ◽  
Vol 9 (6) ◽  
pp. 76
Author(s):  
Kavita Chandramore
Keyword(s):  
Homology Modeling ◽  
Protein Function ◽  
Structural Model ◽  
Query Sequence ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Parasitic Disease ◽  
Loa Loa ◽  
Knowledge Based ◽  
Template Sequence

Objective: A systematic technique for protein modeling offers great assistance in the study of protein function, dynamics, interactions with ligands, other proteins and even in drug discovery and drug design. Subcutaneous filariasis is rare parasitic disease caused by Loa Loa (eye worm) and monosonallastreptoscerca species. Methods: The present study develop three dimensional structure of dihydrofolatereductase present in Loa loa species. For this purpose knowledge based homology modeling is used by using Schrodinger Glide 5.6 software.Results: The procedure involves alignment that maps residues in the query sequence to residues in the template sequence to generate structural model of target, which was further refined and final result validated by using Ramchandran plot.Conclusion: In ramchandran plot majority of the amino acids are in the phi-psi distribution and thedevelop model is reliable and of good quality.

scholarly journals In-silico study of Hesperidin, Epigallocatechin (EGCG ), Kaempferol and Quercetin

2021 ◽  
Author(s):  
Soham Chatterjee ◽  
Smrajit Maiti ◽  
Amrita Bannerjee ◽  
Mehak Kanwar
Keyword(s):  
Spatial Data ◽  
Chemical Structure ◽  
Three Dimensional ◽  
Rna Dependent Rna Polymerase ◽  
X Ray ◽  
X Ray Crystallography ◽  
Wide Range ◽  
In Silico Study ◽  
3Cl Protease ◽  
Conclusive Data

Abstract SARS-Cov-2 or COVID-19 has caused a global disaster and catastrophe which has consequently led to a pandemic for the last two decades, the world has faced coronaviruses similar to SARS-Cov-2 such as SARS-Cov and Mers-Cov. In this study, a wide range of proteins such as Plpro (Papain like Protease), Rdrp (RNA-Dependent-RNA-Polymerase), Mpro or 3cl Protease and Spike Protein. The selected proteins were listed retrieved from RCSB PDB(https://www.rcsb.org/) And Zhang lab (https://www.zhanglab.ccmb.med.umich.edu/COVID-19/) with their corresponding and respective PDB-ID. The 3d Structures or 2D Structures of these molecules were selected on the sole basis of resolved resolution (in Å)of the structures during the X-ray crystallography and Electron Microscopy. Structures were retrieved in .pdb format. The three dimensional ligand molecules were retrieved from PubChem chemical structure In Spatial Data Base (.SDF) format. The respective ligand molecules are; Hesperidin, Kaempferol, Quercetin, Epigallocatechin. This molecular docking shows significant data of polyphenols, flavonoids and bioflavonoids inhibiting SARS-Cov-2 proteins which could lead to conclusive data for treatment of polyphenols, flavonoids and bioflavonoids against SARS-Cov-2.

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