The Novel Approach to the Protein Design: Active Truncated Forms of Human 1-CYS Peroxiredoxin

Nekrasov, A. N.; Radchenko, V. V.; Shuvaeva, T. M.; Новоселов, В. И.; Fesenko, E. E.; Липкин, В. М.

doi:10.1080/07391102.2007.10507133

Cited by 12 publications

(10 citation statements)

References 18 publications

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“…This method is an effective tool for the design of active forms of enzymes or chimeric proteins that combine the enzymatic activities of their wild-type prototypes. This method was successfully used to construct the active forms of certain proteins, e.g, human 1-CYS peroxiredoxin [13] and interleukin-13 antagonist [14]. The method allows for identification of protein structure elements responsible for catalytic activity.…”

Section: Introductionmentioning

confidence: 99%

New insight into the mechanism of mitochondrial cytochrome c function

et al. 2017

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We investigate functional role of the P76GTKMIFA83 fragment of the primary structure of cytochrome c. Based on the data obtained by the analysis of informational structure (ANIS), we propose a model of functioning of cytochrome c. According to this model, conformational rearrangements of the P76GTKMIFA83 loop fragment have a significant effect on conformational mobility of the heme. It is suggested that the conformational mobility of cytochrome c heme is responsible for its optimal orientation with respect to electron donor and acceptor within ubiquinol–cytochrome c oxidoreductase (complex III) and cytochrome c oxidase (complex IV), respectively, thus, ensuring electron transfer from complex III to complex IV. To validate the model, we design several mutant variants of horse cytochrome c with multiple substitutions of amino acid residues in the P76GTKMIFA83 sequence that reduce its ability to undergo conformational rearrangements. With this, we study the succinate–cytochrome c reductase and cytochrome c oxidase activities of rat liver mitoplasts in the presence of mutant variants of cytochrome c. The electron transport activity of the mutant variants decreases to different extent. Resonance Raman spectroscopy (RRS) and surface-enhanced Raman spectroscopy (SERS) data demonstrate, that all mutant cytochromes possess heme with the higher degree of ruffling deformation, than that of the wild-type (WT) cytochrome c. The increase in the ruffled deformation of the heme of oxidized cytochromes correlated with the decrease in the electron transport rate of ubiquinol–cytochrome c reductase (complex III). Besides, all mutant cytochromes have lower mobility of the pyrrol rings and methine bridges, than WT cytochrome c. We show that a decrease in electron transport activity in the mutant variants correlates with conformational changes and reduced mobility of heme porphyrin. This points to a significant role of the P76GTKMIFA83 fragment in the electron transport function of cytochrome c.

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Section: Introductionmentioning

confidence: 99%

New insight into the mechanism of mitochondrial cytochrome c function

et al. 2017

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“…This method is promising for use in the design of recombinant proteins, since the removal or addition of individual branches of the hierarchical tree should not affect the folding of the protein as a whole. Previously, this method was already used for the design of recombinant proteins and solving biotechnological problems [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The ANIS method was confirmed in a number of experimental researches [ 20 , 21 , 22 ]. Subsequently, we used the revealed hierarchical elements for protein design [ 23 , 24 , 25 , 26 ] and for the study of the mechanisms of protein function [ 20 , 21 , 22 ]. It was experimentally shown [ 22 , 23 , 25 , 26 ] that the removal of sequence fragments corresponding to free-standing graphs from the native protein sequence leads to minimal folding distortion of the recombinant protein.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, we used the revealed hierarchical elements for protein design [ 23 , 24 , 25 , 26 ] and for the study of the mechanisms of protein function [ 20 , 21 , 22 ]. It was experimentally shown [ 22 , 23 , 25 , 26 ] that the removal of sequence fragments corresponding to free-standing graphs from the native protein sequence leads to minimal folding distortion of the recombinant protein. In [ 20 , 22 ], using the analysis of hierarchical elements in the protein structure, mechanical models of functioning of protein molecular machines were proposed.…”

Section: Introductionmentioning

confidence: 99%

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Hierarchical Structure of Protein Sequence

Некрасов

Kozmin

Kozyrev

et al. 2021

IJMS

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Most non-communicable diseases are associated with dysfunction of proteins or protein complexes. The relationship between sequence and structure has been analyzed for a long time, and the analysis of the sequences organization in domains and motifs remains an actual research area. Here, we propose a mathematical method for revealing the hierarchical organization of protein sequences. The method is based on the pentapeptide as a unit of protein sequences. Employing the frequency of occurrence of pentapeptides in sequences of natural proteins and a special mathematical approach, this method revealed a hierarchical structure in the protein sequence. The method was applied to 24,647 non-homologous protein sequences with sizes ranging from 50 to 400 residues from the NRDB90 database. Statistical analysis of the branching points of the graphs revealed 11 characteristic values of y (the width of the inscribed function), showing the relationship of these multiple fragments of the sequences. Several examples illustrate how fragments of the protein spatial structure correspond to the elements of the hierarchical structure of the protein sequence. This methodology provides a promising basis for a mathematically-based classification of the elements of the spatial organization of proteins. Elements of the hierarchical structure of different levels of the hierarchy can be used to solve biotechnological and medical problems.

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“…Subsequently, the revealed hierarchical elements were used by us for protein design [31][32][33][34] and for study of the mechanisms of protein function [26][27][28]. It was experimentally shown in [28,31,33,34] that the removal of sequence fragments corresponding to free-standing graphs from the native protein sequence leads to minimal folding distortion of the recombinant protein. In [26,28], using the analysis of hierarchical elements in the protein structure, mechanical models of functioning of protein molecular machines were proposed.…”

Section: Introductionmentioning

confidence: 99%

Hierarchical Structure of Protein Sequence

Некрасов¹,

Kozmin²,

Kozyrev³

et al. 2021

Preprint

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Most non-infectious diseases are associated with dysfunction of proteins or protein complexes. Аssociation between sequence and structure is analyzed since a long time, and analysis of sequence organization in domains and motifs is actual research area. A mathematical method is proposed here to identify the hierarchical organization of protein sequences. The method is based on pentapeptide as a unit of protein sequences. This method was applied on a non-homologous dataset of protein sequences. The analysis revealed 11 hierarchical levels of protein sequence organization, showing the relationship of these multiple fragments of sequences. Using different examples, we illustrated how the fragments of the spatial structure of protein correspond to the elements of the hierarchical structure of the protein sequence. A hierarchical structure is observed in the protein sequence. This methodology is an interesting basis for mathematically based classification of elements of spatial organization of proteins. Elements of the hierarchical structure of different levels of the hierarchy can be used for biotechnological and medical problems.

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The Novel Approach to the Protein Design: Active Truncated Forms of Human 1-CYS Peroxiredoxin

Cited by 12 publications

References 18 publications

New insight into the mechanism of mitochondrial cytochrome c function

New insight into the mechanism of mitochondrial cytochrome c function

Hierarchical Structure of Protein Sequence

Hierarchical Structure of Protein Sequence

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