scholarly journals Counteraction of urea destabilization of protein structure by methylamine osmoregulatory compounds of elasmobranch fishes

1979 ◽  
Vol 183 (2) ◽  
pp. 317-323 ◽  
Author(s):  
Paul H. Yancey ◽  
George N. Somero
Keyword(s):  
Amino Acids ◽  
Protein Structure ◽  
Protein Function ◽  
Tertiary Structure ◽  
Total Concentration ◽  
Amino Acid Sequences ◽  
Protein Amino Acid ◽  
Evolutionary Changes ◽  
Structural And Functional Properties ◽  
Elasmobranch Fishes

Intracellular fluids of marine elasmobranchs (sharks, skates and rays), holocephalans and the coelacanth contain urea at concentrations averaging 0.4m, high enough to significantly affect the structural and functional properties of many proteins. Also present in the cells of these fishes are a family of methylamine compounds, largely trimethylamine N-oxide with some betaine and sarcosine, and certain free amino acids, mainly β-alanine and taurine, whose total concentration is approx. 0.2m. These methylamine compounds and amino acids have been found to be effective stabilizers of protein structure, and, at a 1:2 molar concentration ratio of these compounds to urea, perturbations of protein structure by urea are largely or fully offset. These counteracting effects of solutes on proteins are seen for: (1) thermal stability of protein secondary and tertiary structure (bovine ribonuclease); (2) the rate and extent of enzyme renaturation after acid denaturation (rabbit and shark lactate dehydrogenases); and (3) the reactivity of thiol groups of an enzyme (bovine glutamate dehydrogenase). Attaining osmotic equilibrium with seawater by these fishes has thus involved the selective accumulation of certain nitrogenous metabolites that individually have significant effects on protein structure, but that have virtually no net effects on proteins when these solutes are present at elasmobranch physiological concentrations. These experiments indicate that evolutionary changes in intracellular solute compositions as well as in protein amino acid sequences can have important roles in intracellular protein function.

scholarly journals Different Synergy in Amyloids and Biologically Active Forms of Proteins

2019 ◽  
Vol 20 (18) ◽  
pp. 4436 ◽  
Author(s):  
Piotr Fabian ◽  
Katarzyna Stapor ◽  
Mateusz Banach ◽  
Magdalena Ptak-Kaczor ◽  
Leszek Konieczny ◽  
...  
Keyword(s):  
Amino Acids ◽  
Comparative Analysis ◽  
Protein Structure ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Water Environment ◽  
Biologically Active ◽  
Radius Of Curvature ◽  
Hydrophobic Core ◽  
Structural Form

Protein structure is the result of the high synergy of all amino acids present in the protein. This synergy is the result of an overall strategy for adapting a specific protein structure. It is a compromise between two trends: The optimization of non-binding interactions and the directing of the folding process by an external force field, whose source is the water environment. The geometric parameters of the structural form of the polypeptide chain in the form of a local radius of curvature that is dependent on the orientation of adjacent peptide bond planes (result of the respective Phi and Psi rotation) allow for a comparative analysis of protein structures. Certain levels of their geometry are the criteria for comparison. In particular, they can be used to assess the differences between the structural form of biologically active proteins and their amyloid forms. On the other hand, the application of the fuzzy oil drop model allows the assessment of the role of amino acids in the construction of tertiary structure through their participation in the construction of a hydrophobic core. The combination of these two models—the geometric structure of the backbone and the determining of the participation in the construction of the tertiary structure that is applied for the comparative analysis of biologically active and amyloid forms—is presented.

scholarly journals Oxidant-Mediated Protein Amino Acid Conversion

Antioxidants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 50 ◽  
Author(s):  
Yuichiro Suzuki
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Biological System ◽  
Redox Regulation ◽  
Amino Acid Sequences ◽  
Biological Oxidation ◽  
Oxidation Reactions ◽  
Protein Amino Acid ◽  
Peroxiredoxin 6 ◽  
Protein Molecules

Biological oxidation plays important roles in the pathogenesis of various diseases and aging. Carbonylation is one mode of protein oxidation. It has been reported that amino acids that are susceptible to carbonylation are arginine (Arg), proline (Pro), lysine, and threonine residues. The carbonylation product of both Arg and Pro residues is glutamyl semialdehyde. While chemically the oxidation reactions of neither Pro to glutamyl semialdehyde nor Arg to glutamyl semialdehyde are reversible, experimental results from our laboratory suggest that the biological system may drive the reduction of glutamyl semialdehyde to Pro in the protein structure. Further, glutamyl semialdehyde can be oxidized to become glutamic acid (Glu). Therefore, I hypothesize that biological oxidation post-translationally converts Arg to Pro, Arg to Glu, and Pro to Glu within the protein structure. Our mass spectrometry experiments provided evidence that, in human cells, 5–10% of peroxiredoxin 6 protein molecules have Pro-45 replaced by Glu. This concept of protein amino acid conversion challenges the dogma that amino acid sequences are strictly defined by nucleic acid sequences. I propose that, in the biological system, amino acid replacements can occur post-translationally through redox regulation, and protein molecules with non-DNA coding sequences confer functions.

scholarly journals Supertertiary protein structure affects an allosteric network

2020 ◽  
Author(s):  
Louise Laursen ◽  
Johanna Kliche ◽  
Stefano Gianni ◽  
Per Jemth
Keyword(s):  
Protein Structure ◽  
Protein Function ◽  
Common Property ◽  
Tertiary Structure ◽  
Pdz Domain ◽  
Protein Domains ◽  
Pdz Domains ◽  
Dynamic Changes

AbstractThe notion that protein function is allosterically regulated by structural or dynamic changes in proteins has been extensively investigated in several protein domains in isolation. In particular, PDZ domains have represented a paradigm for these studies, despite providing conflicting results. Furthermore, it is still unknown how the association between protein domains in supramodules, consitituting so-called supertertiary structure, affects allosteric networks. Here, we experimentally mapped the allosteric network in a PDZ:ligand complex, both in isolation and in the context of a supramodular structure, and show that allosteric networks in a PDZ domain are highly dependent on the supertertiary structure in which they are present. This striking sensitivity of allosteric networks to presence of adjacent protein domains is likely a common property of supertertiary structures in proteins. Our findings have general implications for prediction of allosteric networks from primary and tertiary structure and for quantitative descriptions of allostery.

Multi-Objective Evolutionary Algorithm NSGA-II for Protein Structure Prediction using Structural and Energetic Properties

2014 ◽  
Vol 4 (1) ◽  
pp. 43-53 ◽  
Author(s):  
R. A. Faccioli ◽  
L. O. Bortot ◽  
A. C. B. Delbem
Keyword(s):  
Amino Acids ◽  
Protein Structure ◽  
Ab Initio ◽  
Evolutionary Algorithm ◽  
Protein Structure Prediction ◽  
Open Problem ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Nsga Ii ◽  
Energetic Properties

The Protein Structure Prediction (PSP) problem is concerned about the prediction of the native tertiary structure of a protein in respect to its amino acids sequence. PSP is a challenging and computationally open problem. Therefore, several researches and methodologies have been developed for it. In this way, developers are working to integrate frameworks in order to improve their capabilities and make their use more straightforward. This paper presents the application of NSGA-II algorithm using structural and energetic properties of protein. The implementation of this algorithm is based on ProtPred-GROMACS (2PG), an evolutionary framework for PSP. This framework is the integration between ProtPred and GROMACS. Six proteins were used to measure the capacity of ab initio predictions. The results were interesting since in all cases the native-like topology was obtained.

scholarly journals cDNA sequence and heterologous expression of monomeric spinach pullulanase: multiple isomeric forms arise from the same polypeptide

1998 ◽  
Vol 331 (3) ◽  
pp. 937-945 ◽  
Author(s):  
Andreas RENZ ◽  
Stephanie SCHIKORA ◽  
Roland SCHMID ◽  
Jens KOSSMANN ◽  
Erwin BECK
Keyword(s):  
Amino Acids ◽  
Isoelectric Focusing ◽  
Tertiary Structure ◽  
Transit Peptide ◽  
Amino Acid Sequences ◽  
Molecular Forms ◽  
Calculated Molecular Mass ◽  
Post Translational Modifications ◽  
Starting Point ◽  
Spinach Leaf

The spinach pullulanase gene was cloned and sequenced using peptide sequences of the purified enzyme as a starting point and employing PCR techniques and cDNA library screening. Its open reading frame codes for a protein of 964 amino acids which represents a precursor of the pullulanase. The N-terminal transit peptide consists of 65 amino acids, and the mature protein, comprising 899 amino acids, has a calculated molecular mass of 99 kDa. Pullulanase is a member of the α-amylase family. In addition to a characteristic catalytic (β/α)8-barrel domain, it contains a domain, F, that is specific for branching and debranching enzymes. Pullulanase cDNA was expressed in Escherichia coli, and the purified protein was compared with the enzyme from spinach leaves. Identity of the two proteins was confirmed in terms of catalytic properties, N-terminal amino acid sequences and molecular masses. The pullulanase produced by E. coli showed the same microheterogeneity as the spinach leaf enzyme: it could be resolved into two substrate-induced forms by electrophoresis in amylopectin-containing polyacrylamide gels, and, in the absence of substrate, into several free forms (charge isomers) by isoelectric focusing or chromatofocusing. Rechromatofocusing of single free forms resulted in the originally observed pattern of molecular forms. However, heterogeneity of the protein disappeared on isoelectric focusing under completely denaturing conditions when only one protein band was observed. Post-translational modifications such as glycosylation and phosphorylation could be excluded as potential explanations for the protein heterogeneity. Therefore the microheterogeneity of spinach leaf pullulanase results from neither genetic variation nor post-translational modifications, but is a property of the single unmodified gene product. The different interconvertible forms of the pullulanase represent protein populations of different tertiary structure of the same polypeptide.

scholarly journals A sequence embedding method for enzyme optimal condition analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiangjun Li ◽  
Zhixin Dou ◽  
Yuqing Sun ◽  
Lushan Wang ◽  
Bin Gong ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Optimal Condition ◽  
Tertiary Structure ◽  
Structural Information ◽  
Amino Acid Sequences ◽  
Computational Method ◽  
Embedding Method ◽  
Latent Space ◽  
Probabilistic Approximation

Abstract Background An enzyme activity is influenced by the external environment. It is important to have an enzyme remain high activity in a specific condition. A usual way is to first determine the optimal condition of an enzyme by either the gradient test or by tertiary structure, and then to use protein engineering to mutate a wild type enzyme for a higher activity in an expected condition. Results In this paper, we investigate the optimal condition of an enzyme by directly analyzing the sequence. We propose an embedding method to represent the amino acids and the structural information as vectors in the latent space. These vectors contain information about the correlations between amino acids and sites in the aligned amino acid sequences, as well as the correlation with the optimal condition. We crawled and processed the amino acid sequences in the glycoside hydrolase GH11 family, and got 125 amino acid sequences with optimal pH condition. We used probabilistic approximation method to implement the embedding learning method on these samples. Based on these embedding vectors, we design a computational score to determine which one has a better optimal condition for two given amino acid sequences and achieves the accuracy 80% on the test proteins in the same family. We also give the mutation suggestion such that it has a higher activity in an expected environment, which is consistent with the previously professional wet experiments and analysis. Conclusion A new computational method is proposed for the sequence based on the enzyme optimal condition analysis. Compared with the traditional process that involves a lot of wet experiments and requires multiple mutations, this method can give recommendations on the direction and location of amino acid substitution with reference significance for an expected condition in an efficient and effective way.

Similarities in protein amino acid composition in connection with principles of protein evolution

2008 ◽  
Vol 3 (2) ◽  
pp. 205-209
Author(s):  
Yuriy Shckorbatov ◽  
Andrey Berezhnoy
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Program Analysis ◽  
Protein Function ◽  
Amino Acid Sequences ◽  
Protein Amino Acid ◽  
Program Complex ◽  
Common Amino Acid ◽  
Similar Operation

AbstractThe amino acid composition of human alcohol dehydrogenase (ADH) was compared with alcohol dehydrogenases from different organisms and with other proteins. Similar amino acid sequences in human ADH (template protein) and in other proteins were determined by means of an original computer program. Analysis of amino acid motifs reveals that the ADHs from evolutionary more close organisms have more common amino acid sequences. The quantity measure of amino acid similarity was the number of similar motifs in analyzed protein per protein length. This value was measured for ADHs and for different proteins. For ADHs, this quotient was higher than for proteins with different functions; for vertebrates it correlated with evolutionary closeness. The similar operation of motif comparison was made with the help of program complex “MEME”. The analysis of ADHs revealed 4 motifs common to 6 of 10 tested organisms and no such motifs for proteins of different function. The conclusion is that general amino composition is more important for protein function than amino acid order and for enzymes of similar function it better correlates with evolutionary distance between organisms.

scholarly journals A Sequence Embedding Method For Enzyme Optimal Condition Analysis

2019 ◽  
Author(s):  
Xiangjun Li ◽  
Zhixin Dou ◽  
Yuqing Sun ◽  
Lushan Wang ◽  
Bin Gong
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Optimal Condition ◽  
Tertiary Structure ◽  
Amino Acid Sequences ◽  
Computational Method ◽  
Protein Sequence Analysis ◽  
Embedding Method ◽  
Latent Space ◽  
Probabilistic Approximation

Abstract Background: An enzyme activity is influenced by the external environment condition. It is important to have an enzyme remain high activity in a specific condition. A usual way is to first determine the optimal condition of an enzyme by either the gradient test or by tertiary structure, and then to use protein engineering to mutate a wild type enzyme for a higher activity in an expected condition. Results: In this paper, we investigate the optimal condition of an enzyme by directly analyzing the sequence. We propose an embedding method to represent the amino acids and the construct information as vectors in the latent space. These vectors contain information about the correlations between amino acids and sites in the aligned amino acid sequences, as well as the correlations with the optimal conditions. We crawled and processed the amino acid sequence in glycoside hydrolase GH11 family, and got 125 amino acid sequences with optimal pH condition. We used probabilistic approximation method to implement the embedding learning method on these samples. Based on these embedding vectors, we design a computational score to determine the optimal condition for an enzyme and achieves the accuracy 80% on the test proteins in the same family. We also give the mutation suggestion such that it has a higher activity in the expected environment, which is consistent with the professional wet experiments and analysis. Conclusion: A new computational method is proposed for the sequence based enzyme optimal condition analysis. Compared with the traditional process that involves a lot of wet experiments and requires multiple mutations, this method can get the desired protein for an expected condition in an efficient and effective way. Keywords: Protein sequence analysis; Embedding; Bioinformatics

scholarly journals Novel ABCA4 mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing

2018 ◽  
Vol 28 (1) ◽  
pp. 123-126 ◽  
Author(s):  
Nutsuchar Wangtiraumnuay ◽  
Jenina Capasso ◽  
Mai Tsukikawa ◽  
Alex Levin ◽  
Esther Biswas-Fiss
Keyword(s):  
Amino Acids ◽  
Genetic Testing ◽  
Protein Structure ◽  
Protein Function ◽  
Macular Dystrophy ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Variants Of Unknown Significance ◽  
Novel Variants ◽  
Unknown Significance

Purpose: Mutations in the ABCA4 gene result in a broad spectrum of severe retinal degeneration, including Stargardt macular dystrophy, fundus flavimaculatus, autosomal recessive retinitis pigmentosa, and cone-rod dystrophy. In addition to the detection of well-characterized mutations, genetic testing frequently yields novel variants of unknown significance. The purpose of this report is to describe an approach to aid in the assessment of genetic variants of unknown significance. Case report: We report an 11-year-old girl with Stargardt disease harboring novel compound heterozygous deletions of ABCA4 (c.850_857delATTCAAGA and c.6184_6187delGTCT). The pathogenicity of these variants was otherwise unknown. Both deletions introduce premature stop codons and are localized within the open reading frame of ABCA4. The c.850_857delATTCAAGA occurs early in the gene and leads to a significantly truncated protein of only 317 amino acids. The c.6184_6187delGTCT, is localized to the 3’ terminus of the ORF and results in removal of the last 161 out of 2,273 amino acids of ABCA4, including the VFVNFA motif, which has been shown to be critical in ABCA4 protein function. Homology-based protein modeling of ABCA4 harboring this deletion suggests significant alterations in the protein structure and function. Conclusions: Our analyses allowed us to classify novel variants in ABCA4 as being clearly loss-of-function mutations, and thus pathogenic variants. In cases of variants of unknown significance, appraising the protein structure-function consequences of genetic mutations using in silico tools may help to predict the clinical importance of variants of uncertain pathogenicity.

Sign in / Sign up

Export Citation Format

Share Document