scholarly journals Insights into the quaternary association of proteins through structure graphs: a case study of lectins

2005 ◽  
Vol 391 (1) ◽  
pp. 1-15 ◽  
Author(s):  
K. V. Brinda ◽  
Avadhesha Surolia ◽  
Sarawathi Vishveshwara
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Present Review ◽  
Dimensional Structure ◽  
Protein Oligomerization ◽  
Amino Acid Residues ◽  
Sequence Motifs ◽  
Structural Determinants ◽  
Legume Lectin ◽  
Quaternary Structures

The unique three-dimensional structure of both monomeric and oligomeric proteins is encoded in their sequence. The biological functions of proteins are dependent on their tertiary and quaternary structures, and hence it is important to understand the determinants of quaternary association in proteins. Although a large number of investigations have been carried out in this direction, the underlying principles of protein oligomerization are yet to be completely understood. Recently, new insights into this problem have been gained from the analysis of structure graphs of proteins belonging to the legume lectin family. The legume lectins are an interesting family of proteins with very similar tertiary structures but varied quaternary structures. Hence they have become a very good model with which to analyse the role of primary structures in determining the modes of quaternary association. The present review summarizes the results of a legume lectin study as well as those obtained from a similar analysis carried out here on the animal lectins, namely galectins, pentraxins, calnexin, calreticulin and rhesus rotavirus Vp4 sialic-acid-binding domain. The lectin structure graphs have been used to obtain clusters of non-covalently interacting amino acid residues at the intersubunit interfaces. The present study, performed along with traditional sequence alignment methods, has provided the signature sequence motifs for different kinds of quaternary association seen in lectins. Furthermore, the network representation of the lectin oligomers has enabled us to detect the residues which make extensive interactions (‘hubs’) across the oligomeric interfaces that can be targetted for interface-destabilizing mutations. The present review also provides an overview of the methodology involved in representing oligomeric protein structures as connected networks of amino acid residues. Further, it illustrates the potential of such a representation in elucidating the structural determinants of protein–protein association in general and will be of significance to protein chemists and structural biologists.

scholarly journals Structure of Looped Regions in β-α- and α-β-Arches in Abcd-Units of Globular Proteins

2016 ◽  
Vol 11 (2) ◽  
pp. 159-169
Author(s):  
Е.В. Бражников ◽  
E.V. Brazhnikov
Keyword(s):  
Amino Acid ◽  
De Novo ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Motif ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Reverse Turn ◽  
Structure Of Proteins

Conformations of about 600 looped regions (loops) in β-α- and α-β-arches of a structural motif occurring in the abCd-unit of proteins were analyzed. On the whole, 258 abCd-units with a reverse turn of the polypeptide chain (236 PDB files) and 69 abCd-units with a direct turn (65 PDB files) were selected in non-homologous proteins. Four types of arches were studied: β-α- and α-β-ones at a direct turn of the chain; β-α- and α-β-ones at a reverse turn of the chain. For each type of arches, frequencies of loops occurrence of different lengths were determined and corresponding histograms were plotted. It was found that abCd-units with loops up to three amino acid residues long occur most frequently (57 %). In β-α-arches with a direct turn of the chain, loops consisting of two amino acid residues occur most often (44 %) and in 86% cases they have the βmαβαn - conformation. They have no Gly and Pro residues, and in position β there is an Asn residue. In such type of arches, the loops of one residue (βmεαn- or βmαLαn- conformation) contain the Gly residue most frequently. α-β-Arches with a direct turn of the chain have most commonly (18 %) loops of four amino acid residues. In this case, there is no predominant conformation of the loops. In β-α-arches with a reverse turn of the chain, most common are loops of seven amino acid residues (17%), and most part of them (88 %) have the βmαLββααββαn - conformation. α-β-Arches with a reverse turn of the chain contain most frequently (32%) loops of one amino acid residue (all Gly ones) with arch conformations αmεβn or αmαLβn. The above structural analysis of the abCd-unit has useful information for prediction of the three-dimensional structure of proteins and for molecular simulation of the de novo design of protein structures.

Statistical Force-Field for Structural Modeling Using Chemical Cross-Linking/mass Spectrometry Distance Constraints

2018 ◽  
Author(s):  
Allan J. R. Ferrari ◽  
Fabio C. Gozzo ◽  
Leandro Martinez
Keyword(s):  
Mass Spectrometry ◽  
Amino Acid ◽  
Force Field ◽  
Protein Structures ◽  
Protein Structure Determination ◽  
Structural Modeling ◽  
Cross Linking ◽  
Amino Acid Residues ◽  
Distance Constraints ◽  
Chemical Cross Linking

<div><p>Chemical cross-linking/Mass Spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues, which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms. Here, a force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. The force-field can be easily incorporated into current modeling methods and software. In this work, the force-field was implemented within the Rosetta ab initio relax protocol. We show a significant improvement in the quality of the models obtained relative to current strategies for constraint representation. This force-field contributes to the long-desired goal of obtaining the tertiary structures of proteins using XLMS data. Force-field parameters and usage instructions are freely available at http://m3g.iqm.unicamp.br/topolink/xlff <br></p></div><p></p><p></p>

scholarly journals Identification and Analysis of Novel Amino-Acid Sequence Repeats inBacillus anthracisstr.AmesProteome Using Computational Tools

2007 ◽  
Vol 2007 ◽  
pp. 1-23 ◽  
Author(s):  
G. R. Hemalatha ◽  
D. Satyanarayana Rao ◽  
L. Guruprasad
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Protein Sequence ◽  
Amino Acid Residues ◽  
Sequence Motifs ◽  
Computational Tools ◽  
Conserved Sequence ◽  
Conserved Sequence Motifs ◽  
Multiple Copies ◽  
Domain 3

We have identified four repeats and ten domains that are novel in proteins encoded by theBacillus anthracisstr.Amesproteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure.

scholarly journals In-silicoprediction and modeling of theEntamoeba histolyticaproteins: Serine-richEntamoeba histolyticaprotein and 29 kDa Cysteine-rich protease

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3160 ◽  
Author(s):  
Kumar Manochitra ◽  
Subhash Chandra Parija
Keyword(s):  
Amino Acid ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Amino Acid Sequences ◽  
Treatment Modalities ◽  
Bioinformatic Tools ◽  
Complex Protein ◽  
A Cell ◽  
Quaternary Structures

BackgroundAmoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings. There exists an ambiguity in the diagnosis of amoebiasis, and hence there arises a necessity for a better diagnostic approach. Serine-richEntamoeba histolyticaprotein (SREHP), peroxiredoxin and Gal/GalNAc lectin are pivotal inE. histolyticavirulence and are extensively studied as diagnostic and vaccine targets. For elucidating the cellular function of these proteins, details regarding their respective quaternary structures are essential. However, studies in this aspect are scant. Hence, this study was carried out to predict the structure of these target proteins and characterize them structurally as well as functionally using appropriatein-silicomethods.MethodsThe amino acid sequences of the proteins were retrieved from National Centre for Biotechnology Information database and aligned using ClustalW. Bioinformatic tools were employed in the secondary structure and tertiary structure prediction. The predicted structure was validated, and final refinement was carried out.ResultsThe protein structures predicted by i-TASSER were found to be more accurate than Phyre2 based on the validation using SAVES server. The prediction suggests SREHP to be an extracellular protein, peroxiredoxin a peripheral membrane protein while Gal/GalNAc lectin was found to be a cell-wall protein. Signal peptides were found in the amino-acid sequences of SREHP and Gal/GalNAc lectin, whereas they were not present in the peroxiredoxin sequence. Gal/GalNAc lectin showed better antigenicity than the other two proteins studied. All the three proteins exhibited similarity in their structures and were mostly composed of loops.DiscussionThe structures of SREHP and peroxiredoxin were predicted successfully, while the structure of Gal/GalNAc lectin could not be predicted as it was a complex protein composed of sub-units. Also, this protein showed less similarity with the available structural homologs. The quaternary structures of SREHP and peroxiredoxin predicted from this study would provide better structural and functional insights into these proteins and may aid in development of newer diagnostic assays or enhancement of the available treatment modalities.

scholarly journals Selection of sequence motifs and generative Hopfield-Potts models for protein families

2019 ◽  
Author(s):  
Kai Shimagaki ◽  
Martin Weigt
Keyword(s):  
Amino Acid ◽  
Ad Hoc ◽  
Three Dimensional ◽  
Generative Models ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Sequence Motifs ◽  
Restricted Boltzmann Machines ◽  
Potts Models ◽  
Maximum Entropy Models

Statistical models for families of evolutionary related proteins have recently gained interest: in particular pairwise Potts models, as those inferred by the Direct-Coupling Analysis, have been able to extract information about the three-dimensional structure of folded proteins, and about the effect of amino-acid substitutions in proteins. These models are typically requested to reproduce the one- and two-point statistics of the amino-acid usage in a protein family, i.e. to capture the so-called residue conservation and covariation statistics of proteins of common evolutionary origin. Pairwise Potts models are the maximum-entropy models achieving this. While being successful, these models depend on huge numbers of ad hoc introduced parameters, which have to be estimated from finite amount of data and whose biophysical interpretation remains unclear. Here we propose an approach to parameter reduction, which is based on selecting collective sequence motifs. It naturally leads to the formulation of statistical sequence models in terms of Hopfield-Potts models. These models can be accurately inferred using a mapping to restricted Boltzmann machines and persistent contrastive divergence. We show that, when applied to protein data, even 20-40 patterns are sufficient to obtain statistically close-to-generative models. The Hopfield patterns form interpretable sequence motifs and may be used to clusterize amino-acid sequences into functional sub-families. However, the distributed collective nature of these motifs intrinsically limits the ability of Hopfield-Potts models in predicting contact maps, showing the necessity of developing models going beyond the Hopfield-Potts models discussed here.

Purification of large peptides using Chemoselective tags

1999 ◽  
Author(s):  
Paolo Mascagni
Keyword(s):  
Amino Acid ◽  
Synthetic Peptides ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Exchange Chromatography ◽  
Target Sequence ◽  
Coupling Reactions ◽  
Amino Acid Residues ◽  
Quaternary Structures ◽  
Specific Stationary Phase

In solid phase peptide synthesis (SPPS), deletion sequences are generated at each addition of amino acid due to non-quantitative coupling reactions. Their concentration increases exponentially with the length of the peptide chain, and after many cycles not only do they represent a large proportion of the crude preparation, but they can also exhibit physicochemical characteristics similar to the target sequence. Thus, these deletion-sequence contaminants present major problems for removal, or even detection. In general, purification of synthetic peptides by conventional chromatography is based on hydrophobicity differences (using RP-HPLC) and charge differences (using ion-exchange chromatography). For short sequences, the use of one or both techniques is in general sufficient to obtain a product with high purity. However, on increasing the number of amino acid residues, the peptide secondary and progressively tertiary and quaternary structures begin to play an important role and the conformation of the largest peptides can decisively affect their retention behaviour. Furthermore, very closely related impurities such as deletion sequences lacking one or few residues can be chromatographically indistinguishable from the target sequence. Therefore, purification of large synthetic peptides is a complex and time-consuming task that requires the use of several separation techniques with the inevitable dramatic reduction in yields of the final material. Permanent termination (capping) of unreacted chains using a large excess of an acylating agent after each coupling step prevents the formation of deletion sequences and generates N-truncated peptides. However, even under these more favourable conditions, separation of the target sequence from chromatographically similar N-capped polypeptides requires extensive purification. If the target sequence could be specifically and transiently labelled so that the resulting product were selectively recognized by a specific stationary phase, then separation from impurities should be facilitated. This chapter deals with such an approach and in particular with the purification of large polypeptides, assembled by solid phase strategy, using lipophilic and biotin-based 9-fluorenylmethoxycarbonyl (Fmoc) chromatographic probes. Assuming that the formation of deletion sequences is prevented by capping unreacted chains, a reciprocal strategy can be applied that involves functional protection of all polymer-supported peptide chains that are still growing, with a specially chosen affinity reagent or chromatographic probe.

Characteristics of Two Forms of α-Amylases and Structural Implication

1999 ◽  
Vol 65 (10) ◽  
pp. 4652-4658 ◽  
Author(s):  
Kohji Ohdan ◽  
Takashi Kuriki ◽  
Hiroki Kaneko ◽  
Jiro Shimada ◽  
Toshikazu Takada ◽  
...  
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Amylase Gene ◽  
Raw Starch ◽  
Raw Starch Binding ◽  
Terminal Amino ◽  
Carboxyl Terminal

ABSTRACT Complete (Ba-L) and truncated (Ba-S) forms of α-amylases fromBacillus subtilis X-23 were purified, and the amino- and carboxyl-terminal amino acid sequences of Ba-L and Ba-S were determined. The amino acid sequence deduced from the nucleotide sequence of the α-amylase gene indicated that Ba-S was produced from Ba-L by truncation of the 186 amino acid residues at the carboxyl-terminal region. The results of genomic Southern analysis and Western analysis suggested that the two enzymes originated from the same α-amylase gene and that truncation of Ba-L to Ba-S occurred during the cultivation of B. subtilis X-23 cells. Although the primary structure of Ba-S was approximately 28% shorter than that of Ba-L, the two enzyme forms had the same enzymatic characteristics (molar catalytic activity, amylolytic pattern, transglycosylation ability, effect of pH on stability and activity, optimum temperature, and raw starch-binding ability), except that the thermal stability of Ba-S was higher than that of Ba-L. An analysis of the secondary structure as well as the predicted three-dimensional structure of Ba-S showed that Ba-S retained all of the necessary domains (domains A, B, and C) which were most likely to be required for functionality as α-amylase.

scholarly journals Efficacy of Dideoxynucleosides against Human Foamy Virus and Relationship to Its Reverse Transcriptase Amino Acid Sequence and Structure

2001 ◽  
Vol 75 (15) ◽  
pp. 7184-7187 ◽  
Author(s):  
Anne Yvon-Groussin ◽  
Pierre Mugnier ◽  
Philippe Bertin ◽  
Marc Grandadam ◽  
Henri Agut ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Foamy Virus ◽  
Three Dimensional ◽  
Retroviral Vectors ◽  
Dimensional Structure ◽  
Human Foamy Virus ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.

PROTEIN METAL BINDING RESIDUE PREDICTION BASED ON NEURAL NETWORKS

2005 ◽  
Vol 15 (01n02) ◽  
pp. 71-84 ◽  
Author(s):  
CHIN-TENG LIN ◽  
KEN-LI LIN ◽  
CHIH-HSIEN YANG ◽  
I-FANG CHUNG ◽  
CHUEN-DER HUANG ◽  
...  
Keyword(s):  
Neural Networks ◽  
Amino Acid ◽  
Metal Ions ◽  
Metal Binding ◽  
Protein Structures ◽  
Direct Analysis ◽  
Sequence Information ◽  
Amino Acid Residues ◽  
Binding Residue

Over one-third of protein structures contain metal ions, which are the necessary elements in life systems. Traditionally, structural biologists were used to investigate properties of metalloproteins (proteins which bind with metal ions) by physical means and interpreting the function formation and reaction mechanism of enzyme by their structures and observations from experiments in vitro. Most of proteins have primary structures (amino acid sequence information) only; however, the 3-dimension structures are not always available. In this paper, a direct analysis method is proposed to predict the protein metal-binding amino acid residues from its sequence information only by neural networks with sliding window-based feature extraction and biological feature encoding techniques. In four major bulk elements (Calcium, Potassium, Magnesium, and Sodium), the metal-binding residues are identified by the proposed method with higher than 90% sensitivity and very good accuracy under 5-fold cross validation. With such promising results, it can be extended and used as a powerful methodology for metal-binding characterization from rapidly increasing protein sequences in the future.

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