scholarly journals Author Correction: A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kentaro Nakashima ◽  
Shintaro Iwashita ◽  
Takehiro Suzuki ◽  
Chieko Kato ◽  
Toshiyuki Kohno ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Spatial Similarity

scholarly journals A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kentaro Nakashima ◽  
Shintaro Iwashita ◽  
Takehiro Suzuki ◽  
Chieko Kato ◽  
Toshiyuki Kohno ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cultured Cells ◽  
Amino Acid Sequences ◽  
Cross Reaction ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Spatial Similarity ◽  
Target Molecules ◽  
The Cross

Abstract It is critical for development of high-quality antibodies in research and diagnostics to predict accurately their cross-reactivities with “off-target” molecules, which potentially induce false results. Herein, we report a good example of such a cross-reactivity for an off-target due to a stereochemical environment of epitopes, which does not simply depend on amino acid sequences. We found that significant subpopulation of a polyclonal peptide antibody against Bcnt (Bucentaur) (anti-BCNT-C antibody) cross-reacted with a completely different protein, glutamine synthetase (GS), and identified four amino acids, GYFE, in its C-terminal region as the core amino acids for the cross-reaction. Consistent with this finding, the anti-BCNT-C antibody strongly recognized endogenously and exogenously expressed GS in tissues and cultured cells by Western blotting and immunohistochemistry. Furthermore, we elucidated that the cross-reaction is caused by a spatial similarity between the stereochemical environments formed by amino acid residues, including the GYFE of GS and the GYIE of Bcnt, rather than by their primary sequences. These results suggest it is critical to comprehensively analyze antibody interactions with target molecules including off-targets with special attention to the physicochemical environments of epitope-paratope interfaces to decrease the risk of false interpretations of results using antibodies in science and clinical applications.

scholarly journals Inferring amino acid interactions underlying protein function

2017 ◽  
Author(s):  
Victor H. Salinas ◽  
Rama Ranganathan
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Structural Basis ◽  
Evolutionary Divergence ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Physical Constraints ◽  
Spatially Distributed ◽  
Statistical Coupling ◽  
Energetic Interactions

Protein function arises from a poorly defined pattern of cooperative energetic interactions between amino acid residues. Strategies for deducing this pattern have been proposed, but lack of benchmark data has limited experimental verification. Here, we extend deep-mutation technologies to enable measurement of many thousands of pairwise amino acid couplings in members of a protein family. The data show that despite great evolutionary divergence, homologous proteins conserve a sparse, spatially distributed network of cooperative interactions between amino acids that underlies function. This pattern is quantitatively captured in the coevolution of amino acid positions, especially as indicated by the statistical coupling analysis (SCA), providing experimental confirmation of the key tenets of this method. This work establishes a clear link between physical constraints on protein function and sequence analysis, enabling a general practical approach for understanding the structural basis for protein function.

HATODAS II – heavy-atom database system with potentiality scoring

2009 ◽  
Vol 42 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Michihiro Sugahara ◽  
Yukuhiko Asada ◽  
Hiroki Shimada ◽  
Hideyuki Taka ◽  
Naoki Kunishima
Keyword(s):  
Amino Acid ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Solvent Accessibility ◽  
Heavy Atom ◽  
Database System ◽  
Protein Crystals ◽  
Amino Acid Residues ◽  
Sequence Alignments ◽  
Homologous Proteins

HATODAS II is the second version of HATODAS (the Heavy-Atom Database System), which suggests potential heavy-atom reagents for the derivatization of protein crystals. The present expanded database contains 3103 heavy-atom binding sites, which is four times more than the previous version. HATODAS II has three new criteria to evaluate the feasibility of the search results: (1) potentiality scoring for the predicted heavy-atom reagents, (2) exclusion of the disordered amino acid residues based on the secondary structure prediction and (3) consideration of the solvent accessibility of amino acid residues from a homology model. In the point mutation option, HATODAS II suggests possible mutation sites into reactive amino acid residues such as Met, Cys and His, on the basis of multiple sequence alignments of homologous proteins. These new features allow the user to make a well informed decision as to the possible heavy-atom derivatization experiments of protein crystals.

scholarly journals SDPpred: a tool for prediction of amino acid residues that determine differences in functional specificity of homologous proteins

2004 ◽  
Vol 32 (Web Server) ◽  
pp. W424-W428 ◽  
Author(s):  
O. V. Kalinina ◽  
P. S. Novichkov ◽  
A. A. Mironov ◽  
M. S. Gelfand ◽  
A. B. Rakhmaninova
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Functional Specificity

Human cytoplasmic ProX edits mischarged tRNAPro with amino acid but not tRNA specificity

2013 ◽  
Vol 450 (1) ◽  
pp. 243-252 ◽  
Author(s):  
Liang-Liang Ruan ◽  
Xiao-Long Zhou ◽  
Min Tan ◽  
En-Duo Wang
Keyword(s):  
Amino Acid ◽  
Protein Biosynthesis ◽  
Trna Synthetase ◽  
Main Body ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Gene Encoding ◽  
Trna Synthetases ◽  
Editing Domain ◽  
First Time

aaRSs (aminoacyl-tRNA synthetases) are responsible for ensuring the fidelity of the genetic code translation by accurately linking a particular amino acid to its cognate tRNA isoacceptor. To ensure accuracy of protein biosynthesis, some aaRSs have evolved an editing process to remove mischarged tRNA. The hydrolysis of the mischarged tRNA usually occurs in an editing domain, which is inserted into or appended to the main body of the aaRS. In addition, autonomous, editing domain-homologous proteins can also trans-edit mischarged tRNA in concert or in compensating for the editing function of its corresponding aaRS. The freestanding ProX is a homologue of the editing domain of bacterial ProRS (prolyl-tRNA synthetase). In the present study, we cloned for the first time a gene encoding HsProX (human cytoplasmic ProX) and purified the expressed recombinant protein. The catalytic specificity of HsProX for non-cognate amino acids and identity elements on tRNAPro for editing were also investigated. We found that HsProX could deacylate mischarged Ala-tRNAPro, but not Cys-HstRNAUGGPro, and specifically targeted the alanine moiety of Ala-tRNAPro. The importance of the CCA76 end of the tRNA for deacylation activity and key amino acid residues in HsProX for its editing function were also identified.

The Amino Acid Sequence of Streptomyces griseus Protease A: The Peptic Peptides

1971 ◽  
Vol 49 (10) ◽  
pp. 1083-1097 ◽  
Author(s):  
P. Johnson ◽  
L. B. Smillie
Keyword(s):  
Amino Acid ◽  
Streptomyces Griseus ◽  
Disulfide Bridge ◽  
Exchange Chromatography ◽  
Amino Acid Sequences ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Acidic Peptide ◽  
Dowex 1 ◽  
Peptide Fractions

The peptic peptides of Streptomyces griseus Protease A (excluding the previously characterized disulfide bridge peptic peptides) were fractionated into basic, neutral, and neutral plus acidic peptide fractions by chromatography on Dowex 1 × 2. These three peptide fractions were then fractionated by cation-exchange chromatography on Chromobead P resin using the Technicon autoanalyzer system. Following further purifications on paper, the amino acid compositions and sequences of the peptic peptides were determined. The N-terminal sequence of Protease A has been identified as Ile–Ala–Gly–Gly–Glu–Ala. The numbers of amino acid residues obtained from the amino acid sequences reported are in agreement with those numbers obtained from amino acid analysis of the total protein in the cases of tryptophan, methionine, histidine, proline, phenylalanine, and glutamic acid. Some of the results suggest either the presence of nonidentical but highly homologous proteins in the Protease A preparation or the possibility of repeating sequences in a single molecular species.

Structural Relationship Between Human Salivary Histatins

1990 ◽  
Vol 69 (1) ◽  
pp. 2-6 ◽  
Author(s):  
R.F. Troxler ◽  
G.D. Offner ◽  
T. Xu ◽  
J.C. Vanderspek ◽  
F.G. Oppenheim
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Pathogenic Yeast ◽  
Histatin 5 ◽  
Structural Relationships ◽  
Carboxyl Terminal ◽  
Relationship Of ◽  
First Time

Histatins are a group of electrophoretically distinct histidine-rich polypeptides with microbicidal activity found in human parotid and submandibular gland secretions. Recently, we have shown that histatins 1, 3, and 5 are homologous proteins that consist of 38, 32, and 24 amino acid residues, respectively, and that these polypeptides kill the pathogenic yeast, Candida albicans. We now describe the isolation and structural characterization of histatins 2, 4, 6, and 7-12, the remaining members of this group of polypeptides. Histatin 2 was found to be identical to the carboxyl terminal 26 residues of histatin 1; histatin 4 was found to be identical to the carboxyl terminal 20 residues of histatin 3; and histatin 6 was found to be identical to histatin 5, but contained an additional carboxyl terminal arginine residue. The amino acid sequences of histatins 7-12 formally correspond to residues 12-24, 13-24, 12-25, 13-25, 5-11, and 5-12, respectively, of histatin 3, but could also arise proteolytically from histatin 5 or 6. These results establish, for the first time, the complete structural relationships between all members of this group of microbicidal proteins in human parotid saliva. The relationship of histatins to one another is discussed in the context of their genetic origin, biosynthesis and secretion into the oral cavity, and potential as reagents in anti-candidal studies.

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.

COMPACTNESS DETERMINES PROTEIN FOLDING TYPE

2008 ◽  
Vol 06 (04) ◽  
pp. 667-680 ◽  
Author(s):  
OXANA V. GALZITSKAYA ◽  
NATALYA S. BOGATYREVA ◽  
DMITRY N. IVANKOV
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Size Range ◽  
Accessible Surface Area ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Folding Rates ◽  
The Difference ◽  
Accessible Surface ◽  
Ideal Sphere

We have demonstrated here that protein compactness, which we define as the ratio of the accessible surface area of a protein to that of the ideal sphere of the same volume, is one of the factors determining the mechanism of protein folding. Proteins with multi-state kinetics, on average, are more compact (compactness is 1.49 ± 0.02 for proteins within the size range of 101–151 amino acid residues) than proteins with two-state kinetics (compactness is 1.59 ± 0.03 for proteins within the same size range of 101–151 amino acid residues). We have shown that compactness for homologous proteins can explain both the difference in folding rates and the difference in folding mechanisms.

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