Molecular recognition in protein families: A database of aligned three-dimensional structures of related proteins

1993 ◽  
Vol 21 (3) ◽  
pp. 597-604 ◽  
Author(s):  
John P. Overington ◽  
Zhan-Yang Zhu ◽  
Andrej Šali ◽  
Mark S. Johnson ◽  
Ramanathan Sowdhamini ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Three Dimensional ◽  
Protein Families ◽  
Related Proteins

scholarly journals Frequent subgraph mining for biologically meaningful structural motifs

2020 ◽  
Author(s):  
Sebastian Keller ◽  
Pauli Miettinen ◽  
Olga V. Kalinina
Keyword(s):  
Ligand Binding ◽  
Three Dimensional ◽  
Structural Motif ◽  
Frequent Subgraph Mining ◽  
Protein Families ◽  
Biologically Relevant ◽  
Subgraph Mining ◽  
Frequent Subgraph ◽  
Related Proteins ◽  
Jelly Roll

AbstractIdentification of biologically relevant motifs in proteins is a long-standing problem in bioinformatics, especially when considering distantly related proteins where sequence analysis alone becomes increasingly difficult. Here we present a novel approach to identify such motifs in protein three-dimensional structures without depending on sequence alignment by representing structures as graphs in the form of residue interaction networks and employing a modified frequent subgraph mining algorithm. These networks represent residues as vertices while contacts between residues are denoted by edges labeled with Euclidean distances. We use frequent subgraph mining to determine all subgraphs that are subgraph isomorphic to, i.e. are contained in, at least a given number of such networks generated from structures in the same protein family. For this we introduce two extensions of the classical frequent subgraph mining: approximate matching of distance-based labels to account for small variations between protein structures and scoring as well as score-based filtering of subgraphs in order to identify structurally conserved motifs and to counteract the expanding size of the search space. This approach was then validated by demonstrating that it can rediscover previously characterized functionally important structural motifs in selected protein families. For further validation we show that it is also able to identify motifs that correspond to patterns in the PROSITE database. We then applied our approach to all superfamilies in the SCOP database and found an enrichment of residues in the ligand binding site in the discovered motifs evidencing their functional importance. Finally we use the approach to discover a novel structural motif in jelly-roll capsid proteins found in members of the picornavirus-like superfamily. This is presented together with an efficient open source implementation of the algorithm called RINminer.Author summaryAs the evolutionary distance between proteins increases, their sequence identity drops rapidly, whereas functionally important sequence motifs and three-dimensional (3D) structural scaffold, in which they are embedded, are more conserved. We developed an approach that automatically identifies such motifs by converting protein 3D structures into a set of graphs and then employing the frequent subgraph mining framework. In these graphs, residues are represented as vertices, and if two residues interact in the corresponding protein 3D structure, they are connected by an edge labeled with the Euclidean distance between the residues. In the classical setting of frequent subgraph mining, all subgraphs from a database of graphs are enumerated and the ones that are exactly found, i.e. are subgraph isomorphic, in more than a certain number of graphs are listed as supported. Our approach introduces two new concepts: approximately isomorphic subgraphs and an efficient scoring scheme that allows to retain only biologically relevant subgraph in the enumeration step. Approximate isomorphism allows edge labels not to match exactly, and thus account for natural deviations between 3D structures of related proteins. With our approach, we were able to automatically rediscover known motifs from PROSITE, as well as in three well-studied extremely diverse protein families. We predicted functionally important residues in SCOP superfamilies and demonstrated that they tend to lie in structurally meaningful regions: ligand-binding sites and protein core. Additionally, we present a previously unreported structural motif in jelly-roll viral capsids.

A Three-Dimensional Tetraphenylethylene-Based Fluorescence Covalent Organic Framework for Molecular Recognition

2020 ◽  
Author(s):  
Junxia Ren ◽  
Yaozu Liu ◽  
Xin Zhu ◽  
Yangyang Pan ◽  
Yujie Wang ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Fluorescence Probe ◽  
Three Dimensional ◽  
Hazardous Substances ◽  
Covalent Organic Framework ◽  
Highly Sensitive ◽  
Volatile Organic ◽  
Polycyclic Aromatic ◽  
Better Than ◽  
Organic Framework

<p><a></a><a></a><a></a><a></a><a></a><a></a><a></a><a>The development of highly-sensitive recognition of </a><a></a><a></a><a></a><a></a><a>hazardous </a>chemicals, such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs), is of significant importance because of their widespread social concerns related to environment and human health. Here, we report a three-dimensional (3D) covalent organic framework (COF, termed JUC-555) bearing tetraphenylethylene (TPE) side chains as an aggregation-induced emission (AIE) fluorescence probe for sensitive molecular recognition.<a></a><a> </a>Due to the rotational restriction of TPE rotors in highly interpenetrated framework after inclusion of dimethylformamide (DMF), JUC-555 shows impressive AIE-based strong fluorescence. Meanwhile, owing to the large pore size (11.4 Å) and suitable intermolecular distance of aligned TPE (7.2 Å) in JUC-555, the obtained material demonstrates an excellent performance in the molecular recognition of hazardous chemicals, e.g., nitroaromatic explosives, PAHs, and even thiophene compounds, via a fluorescent quenching mechanism. The quenching constant (<i>K</i><sub>SV</sub>) is two orders of magnitude better than those of other fluorescence-based porous materials reported to date. This research thus opens 3D functionalized COFs as a promising identification tool for environmentally hazardous substances.</p>

scholarly journals Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins

1993 ◽  
Vol 2 (3) ◽  
pp. 366-382 ◽  
Author(s):  
Miroslaw Cygler ◽  
Joseph D. Schrag ◽  
Joel L. Sussman ◽  
Michal Harel ◽  
Israel Silman ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Large Family ◽  
Sequence Conservation ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Related Proteins

scholarly journals Evolution of polymer formation within the actin superfamily

2017 ◽  
Vol 28 (19) ◽  
pp. 2461-2469 ◽  
Author(s):  
Patrick R. Stoddard ◽  
Tom A. Williams ◽  
Ethan Garner ◽  
Buzz Baum
Keyword(s):  
Convergent Evolution ◽  
Atp Hydrolysis ◽  
Linear Polymers ◽  
Related Protein ◽  
Protein Families ◽  
Structure And Dynamics ◽  
Polymer Formation ◽  
Filament Structure ◽  
Related Proteins ◽  
Actin Superfamily

While many are familiar with actin as a well-conserved component of the eukaryotic cytoskeleton, it is less often appreciated that actin is a member of a large superfamily of structurally related protein families found throughout the tree of life. Actin-related proteins include chaperones, carbohydrate kinases, and other enzymes, as well as a staggeringly diverse set of proteins that use the energy from ATP hydrolysis to form dynamic, linear polymers. Despite differing widely from one another in filament structure and dynamics, these polymers play important roles in ordering cell space in bacteria, archaea, and eukaryotes. It is not known whether these polymers descended from a single ancestral polymer or arose multiple times by convergent evolution from monomeric actin-like proteins. In this work, we provide an overview of the structures, dynamics, and functions of this diverse set. Then, using a phylogenetic analysis to examine actin evolution, we show that the actin-related protein families that form polymers are more closely related to one another than they are to other nonpolymerizing members of the actin superfamily. Thus all the known actin-like polymers are likely to be the descendants of a single, ancestral, polymer-forming actin-like protein.

scholarly journals Conserved Structure and Function in the Granulysin and NK-Lysin Peptide Family

2005 ◽  
Vol 73 (10) ◽  
pp. 6332-6339 ◽  
Author(s):  
Charlotte M. A. Linde ◽  
Susanna Grundström ◽  
Erik Nordling ◽  
Essam Refai ◽  
Patrick J. Brennan ◽  
...  
Keyword(s):  
Mycobacterium Smegmatis ◽  
Three Dimensional ◽  
Antimycobacterial Activity ◽  
Structure And Function ◽  
Loop Structure ◽  
E Coli ◽  
Short Loop ◽  
Peptide Family ◽  
And Function ◽  
Related Proteins

ABSTRACT Granulysin and NK-lysin are homologous bactericidal proteins with a moderate residue identity (35%), both of which have antimycobacterial activity. Short loop peptides derived from the antimycobacterial domains of granulysin, NK-lysin, and a putative chicken NK-lysin were examined and shown to have comparable antimycobacterial but variable Escherichia coli activities. The known structure of the NK-lysin loop peptide was used to predict the structure of the equivalent peptides of granulysin and chicken NK-lysin by homology modeling. The last two adopted a secondary structure almost identical to that of NK-lysin. All three peptides form very similar three-dimensional (3-D) architectures in which the important basic residues assume the same positions in space. The basic residues in granulysin are arginine, while those in NK-lysin and chicken NK-lysin are a mixture of arginine and lysine. We altered the ratio of arginine to lysine in the granulysin fragment to examine the importance of basic residues for antimycobacterial activity. The alteration of the amino acids reduced the activity against E. coli to a larger extent than that against Mycobacterium smegmatis. In granulysin, the arginines in the loop structure are not crucial for antimycobacterial activity but are important for cytotoxicity. We suggest that the antibacterial domains of the related proteins granulysin, NK-lysin, and chicken NK-lysin have conserved their 3-D structure and their function against mycobacteria.

scholarly journals Chaperones and Proteostasis: Role in Parkinson’s Disease

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 24 ◽  
Author(s):  
Neha Joshi ◽  
Atchaya Raveendran ◽  
Shirisha Nagotu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Three Dimensional ◽  
Cellular Protein ◽  
The Body ◽  
Dimensional Structure ◽  
Protein Homeostasis ◽  
Altered Expression ◽  
And Function ◽  
Related Proteins

Proper folding to attain a defined three-dimensional structure is a prerequisite for the functionality of a protein. Improper folding that eventually leads to formation of protein aggregates is a hallmark of several neurodegenerative disorders. Loss of protein homeostasis triggered by cellular stress conditions is a major contributing factor for the formation of these toxic aggregates. A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis. Expanding the body of evidence highlights the role of chaperones as central mediators in the formation, de-aggregation and degradation of the aggregates. Altered expression and function of chaperones is associated with many neurodegenerative diseases including Parkinson’s disease. Several studies indicate that chaperones are at the center of the cause and effect cycle of this disease. An overview of the various chaperones that are associated with homeostasis of Parkinson’s disease-related proteins and their role in pathogenicity will be discussed in this review.

scholarly journals Yosshi: a web-server for disulfide engineering by bioinformatic analysis of diverse protein families

2019 ◽  
Vol 47 (W1) ◽  
pp. W308-W314 ◽  
Author(s):  
Dmitry Suplatov ◽  
Daria Timonina ◽  
Yana Sharapova ◽  
Vytas Švedas
Keyword(s):  
Disulfide Bonds ◽  
Web Server ◽  
Bioinformatic Analysis ◽  
Protein Families ◽  
Sequence Alignments ◽  
Interactive Analysis ◽  
Functionally Diverse ◽  
Available Information ◽  
Related Proteins

Abstract Disulfide bonds play a significant role in protein stability, function or regulation but are poorly conserved among evolutionarily related proteins. The Yosshi can help to understand the role of S–S bonds by comparing sequences and structures of homologs with diverse properties and different disulfide connectivity patterns within a common structural fold of a superfamily, and assist to select the most promising hot-spots to improve stability of proteins/enzymes or modulate their functions by introducing naturally occurring crosslinks. The bioinformatic analysis is supported by the integrated Mustguseal web-server to construct large structure-guided sequence alignments of functionally diverse protein families that can include thousands of proteins based on all available information in public databases. The Yosshi+Mustguseal is a new integrated web-tool for a systematic homology-driven analysis and engineering of S–S bonds that facilitates a broader interpretation of disulfides not just as a factor of structural stability, but rather as a mechanism to implement functional diversity within a superfamily. The results can be downloaded as a content-rich PyMol session file or further studied online using the HTML5-based interactive analysis tools. Both web-servers are free and open to all users at https://biokinet.belozersky.msu.ru/yosshi and there is no login requirement.

scholarly journals Structurally inherent antigenic sites. Localization of the antigenic sites of the α-chain of human haemoglobin in three host species by a comprehensive synthetic approach

1982 ◽  
Vol 203 (1) ◽  
pp. 201-208 ◽  
Author(s):  
A L Kazim ◽  
M Z Atassi
Keyword(s):  
Primary Structure ◽  
Host Species ◽  
Three Dimensional ◽  
Antigenic Structure ◽  
Synthetic Approach ◽  
Human Haemoglobin ◽  
Alpha Chain ◽  
Antigenic Sites ◽  
Full Profile ◽  
Related Proteins

The antigenic structure of the alpha-chain of human haemoglobin was studied by a synthetic approach consisting of the synthesis of a series of consecutive overlapping peptides that together systematically represent the entire primary structure of the protein. This approach enabled the identification of a full profile of immunochemically active alpha-chain peptides and the localization of its major ‘continuous’ antigenic sites. Antibodies to haemoglobin raised in each of three different species (goat, rabbit and mouse) recognize similar sites on the alpha-chain. Further, the molecular locations of these sites coincide with alpha-chain regions extrapolated from antigenic sites of the conformationally similar myoglobin molecule. These findings support our earlier proposed concept of ‘structurally inherent antigenic sites’, namely that antigenicity is conferred on certain surface regions of proteins by virtue of their three-dimensional locations. Thus the antigenic sites of conformationally related proteins are likely to have similar molecular locations.

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