scholarly journals Beyond History: The List of The Most Well Studied Human Protein Structures

2020 ◽  
Author(s):  
Zhenlu Li ◽  
Matthias Buck
Keyword(s):  
Protein Structures ◽  
Protein Sequences ◽  
Human Protein ◽  
Current Status ◽  
Protein Database ◽  
X Ray ◽  
X Ray Crystallography ◽  
Protein Biophysics ◽  
The Relationship ◽  
Past Trend

Of 20,000 or so canonical human protein sequences, as of July 2020, 6,747 proteins have had their full or partial medium to high-resolution structures determined by x-ray crystallography or other methods. Which of these proteins dominate the protein database (the PDB) and why? In this paper, we list the 272 top protein structures based on the number of their PDB depositions. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trend and current status for protein science. We briefly discuss the relationship which some of the prominent protein structures have with protein biophysics research and mention their relevance to human diseases. The information may inspire researchers who are new to protein science, but it also provides a year 2020 snap-shot for the state of protein science.

scholarly journals Identification of unknown proteins in X-ray crystallography and cryo-EM

2021 ◽  
Author(s):  
Grzegorz Chojnowski ◽  
Adam J. Simpkin ◽  
Diego A. Leonardo ◽  
Wolfram Seifert-Davila ◽  
Dan E. Vivas-Ruiz ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Structures ◽  
Protein Sequences ◽  
Protein Structure Determination ◽  
Natural Sources ◽  
X Ray ◽  
X Ray Crystallography ◽  
Unknown Protein ◽  
Automated Pipeline ◽  
Unknown Sequence

AbstractAlthough experimental protein structure determination usually targets known proteins, chains of unknown sequence are often encountered. They can be purified from natural sources, appear as an unexpected fragment of a well characterized protein or as a contaminant. Regardless of the source of the problem, the unknown protein always requires tedious characterization. Here we present an automated pipeline for the identification of protein sequences from cryo-EM reconstructions and crystallographic data. We present the method’s application to characterize the crystal structure of an unknown protein purified from a snake venom. We also show that the approach can be successfully applied to the identification of protein sequences and validation of sequence assignments in cryo-EM protein structures.

scholarly journals findMySequence: a neural-network-based approach for identification of unknown proteins in X-ray crystallography and cryo-EM

IUCrJ ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Grzegorz Chojnowski ◽  
Adam J. Simpkin ◽  
Diego A. Leonardo ◽  
Wolfram Seifert-Davila ◽  
Dan E. Vivas-Ruiz ◽  
...  
Keyword(s):  
Neural Network ◽  
Protein Structures ◽  
Protein Sequences ◽  
Protein Structure Determination ◽  
Natural Sources ◽  
X Ray ◽  
X Ray Crystallography ◽  
Unknown Protein ◽  
Automated Pipeline ◽  
Unknown Sequence

Although experimental protein-structure determination usually targets known proteins, chains of unknown sequence are often encountered. They can be purified from natural sources, appear as an unexpected fragment of a well characterized protein or appear as a contaminant. Regardless of the source of the problem, the unknown protein always requires characterization. Here, an automated pipeline is presented for the identification of protein sequences from cryo-EM reconstructions and crystallographic data. The method's application to characterize the crystal structure of an unknown protein purified from a snake venom is presented. It is also shown that the approach can be successfully applied to the identification of protein sequences and validation of sequence assignments in cryo-EM protein structures.

scholarly journals Solvent Accessibility of Residues Undergoing Pathogenic Variations in Humans: From Protein Structures to Protein Sequences

2021 ◽  
Vol 7 ◽  
Author(s):  
Castrense Savojardo ◽  
Matteo Manfredi ◽  
Pier Luigi Martelli ◽  
Rita Casadio
Keyword(s):  
Solvent Accessibility ◽  
Protein Structures ◽  
Three Dimensional ◽  
Protein Sequences ◽  
Large Data ◽  
Human Protein ◽  
Dimensional Structure ◽  
Wild Type ◽  
Solvent Exposure ◽  
Data Set

Solvent accessibility (SASA) is a key feature of proteins for determining their folding and stability. SASA is computed from protein structures with different algorithms, and from protein sequences with machine-learning based approaches trained on solved structures. Here we ask the question as to which extent solvent exposure of residues can be associated to the pathogenicity of the variation. By this, SASA of the wild-type residue acquires a role in the context of functional annotation of protein single-residue variations (SRVs). By mapping variations on a curated database of human protein structures, we found that residues targeted by disease related SRVs are less accessible to solvent than residues involved in polymorphisms. The disease association is not evenly distributed among the different residue types: SRVs targeting glycine, tryptophan, tyrosine, and cysteine are more frequently disease associated than others. For all residues, the proportion of disease related SRVs largely increases when the wild-type residue is buried and decreases when it is exposed. The extent of the increase depends on the residue type. With the aid of an in house developed predictor, based on a deep learning procedure and performing at the state-of-the-art, we are able to confirm the above tendency by analyzing a large data set of residues subjected to variations and occurring in some 12,494 human protein sequences still lacking three-dimensional structure (derived from HUMSAVAR). Our data support the notion that surface accessible area is a distinguished property of residues that undergo variation and that pathogenicity is more frequently associated to the buried property than to the exposed one.

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

scholarly journals Structure and function of cement proteins in human adenovirus

2014 ◽  
Vol 70 (a1) ◽  
pp. C1603-C1603
Author(s):  
Vijay Reddy ◽  
Glen Nemerow
Keyword(s):  
Protein Structures ◽  
Human Adenovirus ◽  
Icosahedral Symmetry ◽  
Virion Assembly ◽  
X Ray ◽  
X Ray Crystallography ◽  
Capsid Shell ◽  
Multiple Copies ◽  
And Function ◽  
Cement Protein

Human adenoviruses (HAdVs) are large (~150nm in diameter, 150MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause respiratory, ocular, and enteric diseases. The capsid shell of adenovirus (Ad) comprises multiple copies of three major capsid proteins (MCP: hexon, penton base and fiber) and four minor/cement proteins (IIIa, VI, VIII and IX) that are organized with pseudo T=25 icosahedral symmetry. In addition, six other proteins (V, VII, μ, IVa2, terminal protein and protease) are encapsidated along with the 36Kb dsDNA genome inside the capsid. The crystal structures of all three MCPs are known and so is their organization in the capsid from prior X-ray crystallography and cryoEM analyses. However structures and locations of various cement proteins are of considerable debate. We have determined and refined the structure of an entire human adenovirus employing X-ray crystallpgraphic methods at 3.8Å resolution. Adenovirus cement proteins play crucial roles in virion assembly, disassembly, cell entry and infection. Based on the refined crystal structure of adenovirus, we have determined the structure of the cement protein VI, a key membrane-lytic molecule and its associations with proteins V and VIII, which together glue peripentonal hexons beneath vertex region and connect them to rest of the capsid. Following virion maturation, the cleaved N-terminal pro-peptide of VI is observed deep in the peripentonal hexon cavity, detached from the membrane-lytic domain. Furthermore, we have significantly revised the recent cryoEM models for proteins IIIa and IX and both are located on the capsid exterior. Together, the cement proteins exclusively stabilize the hexon shell, thus rendering penton vertices the weakest links of the adenovirus capsid. Adenovirus cement protein structures reveal the molecular basis of the maturation cleavage of VI that is needed for endosome rupture and delivery of the virion into cytoplasm.

scholarly journals Bence Jones KWR protein structures determined by X-ray crystallography

2007 ◽  
Vol 63 (7) ◽  
pp. 780-792 ◽  
Author(s):  
Debora L. Makino ◽  
Agnes H. Henschen-Edman ◽  
Steven B. Larson ◽  
Alexander McPherson
Keyword(s):  
Protein Structures ◽  
X Ray ◽  
X Ray Crystallography

Ligandensubstitution an cis-Mo(CO)2(PPh3)2(MeCN)(η2-SO2), Kristall- und Molekülstruktur von cis-Mo(CO)2(PMe3)3(η2-SO2) / Ligand Substitution at cis-Mo(CO)2(PPh3)2(MeCN)(η2-SO2), Crystal and Molecular Structure of cis-Mo(CO)2(PMe3)3(η2-SO2)

1986 ◽  
Vol 41 (10) ◽  
pp. 1211-1218 ◽  
Author(s):  
Franz-Erich Baumann ◽  
Christian Burschka ◽  
Wolfdieter A . Schenk
Keyword(s):  
Molecular Structure ◽  
Crystal And Molecular Structure ◽  
Ligand Substitution ◽  
X Ray ◽  
X Ray Crystallography ◽  
Donor And Acceptor ◽  
The Relationship ◽  
Bonding Mode

Abstract Mo(CO)2(PPh3)2(MeCN)(η2-SO2), reacts with a number of unidentate or tridentate phosphines with displacement of both MeCN and PPh3. Mixtures of up to three different isomers are obtained the structures of which are assigned by IR , 1H, 13C, and 31PNMR , and in one case by X-ray crystallography. The results support earlier observations concerning the relationship between the disposition of donor and acceptor ligands around the metal and the bonding mode of SO2 .

scholarly journals xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures

2014 ◽  
Vol 70 (9) ◽  
pp. 2344-2355 ◽  
Author(s):  
Ryan McGreevy ◽  
Abhishek Singharoy ◽  
Qufei Li ◽  
Jingfen Zhang ◽  
Dong Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Large Scale ◽  
Protein Structures ◽  
Data Bank ◽  
Real Space ◽  
Low Resolution ◽  
X Ray ◽  
X Ray Crystallography ◽  
Atomic Structures ◽  
Electron Density Map

X-ray crystallography remains the most dominant method for solving atomic structures. However, for relatively large systems, the availability of only medium-to-low-resolution diffraction data often limits the determination of all-atom details. A new molecular dynamics flexible fitting (MDFF)-based approach, xMDFF, for determining structures from such low-resolution crystallographic data is reported. xMDFF employs a real-space refinement scheme that flexibly fits atomic models into an iteratively updating electron-density map. It addresses significant large-scale deformations of the initial model to fit the low-resolution density, as tested with synthetic low-resolution maps of D-ribose-binding protein. xMDFF has been successfully applied to re-refine six low-resolution protein structures of varying sizes that had already been submitted to the Protein Data Bank. Finally,viasystematic refinement of a series of data from 3.6 to 7 Å resolution, xMDFF refinements together with electrophysiology experiments were used to validate the first all-atom structure of the voltage-sensing protein Ci-VSP.

Introduction

2018 ◽  
Author(s):  
Eaton E. Lattman ◽  
Thomas D. Grant ◽  
Edward H. Snell
Keyword(s):  
Structural Biology ◽  
Single Molecule ◽  
Small Angle ◽  
Structural Information ◽  
Complementary Technique ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Future ◽  
The Relationship ◽  
Basic Level

This chapter provides an introduction to small angle solution scattering with particular reference to the complementary technique of X-ray crystallography and the relationship between the two. It describes at its most basic level the theoretical underpinnings of solution scattering starting from a single molecule and how this information is sampled in crystals versus in solution. A brief introduction is given to some of the primary types of structural information that can be obtained from experiments. The chapter concludes discussing some of the most common applications of the technique in structural biology, and where the future is likely headed.

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