Correlated mutations in hydroxysteroid dehydrogenases family

2017 ◽  
Vol 13 (1) ◽  
Author(s):  
Agata Żyźniewska ◽  
Jacek Leluk ◽  
Gabriela Żaroffe
Keyword(s):  
Amino Acid ◽  
Consensus Sequence ◽  
Hydroxysteroid Dehydrogenase ◽  
Amino Acid Sequences ◽  
Multiple Sequence ◽  
Hydroxysteroid Dehydrogenases ◽  
Uniprot Database ◽  
Correlated Mutations ◽  
Almost All ◽  
Degree Of Similarity

AbstractBackgroundHydroxysteroid dehydrogenase enzymes belong to the short-chain dehydrogenase/reductase (SDR) superfamily and aldo-keto reductases (AKRs). SDR is involved in the metabolism of many compounds (hormones, lipids, etc.) and is present in almost all studied genomes. Two hundred members of hydroxysteroid dehydrogenases have been analysed in terms of natural mutational variability. The second superfamily comprises AKR superfamily group enzymes whose function is catalysing the oxidation and reduction of many substrates by binding NAD(P)H as a cofactor. This kind of study is the first approach for the hydroxysteroid dehydrogenase family. This information grants practical meaning to designing potential specific drugs to fight specific diseases caused by mutations.MethodsIn the research, amino acid sequences of representatives of the hydroxysteroid dehydrogenase family were extracted from the UniProt database. In total, the analysed 200 sequences with the highest degree of similarity were shown by BLAST searches. In the sequence analyses, we used the following software: ClustalX (multiple sequence alignment), Consensus Constructor (creating consensus sequence), and CORM (finding correlated mutations).ResultsThe CORM program identified potential sites of correlated mutations in hydroxysteroid dehydrogenases. This program generated 18 tables of results that contain the amino acid positions of mutations. Seven of these are presented in this paper.ConclusionsThe primary structure of the hydroxysteroid dehydrogenase family shows high variation.

scholarly journals Post-Alignment Adjustment and Its Automation

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1809
Author(s):  
Xuhua Xia
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Position Weight Matrix ◽  
Pairwise Alignment ◽  
Amino Acid Sequences ◽  
Weight Matrix ◽  
Multiple Sequence ◽  
Manual Adjustment ◽  
Alignment Errors ◽  
Almost All

Multiple sequence alignment (MSA) is the basis for almost all sequence comparison and molecular phylogenetic inferences. Large-scale genomic analyses are typically associated with automated progressive MSA without subsequent manual adjustment, which itself is often error-prone because of the lack of a consistent and explicit criterion. Here, I outlined several commonly encountered alignment errors that cannot be avoided by progressive MSA for nucleotide, amino acid, and codon sequences. Methods that could be automated to fix such alignment errors were then presented. I emphasized the utility of position weight matrix as a new tool for MSA refinement and illustrated its usage by refining the MSA of nucleotide and amino acid sequences. The main advantages of the position weight matrix approach include (1) its use of information from all sequences, in contrast to other commonly used methods based on pairwise alignment scores and inconsistency measures, and (2) its speedy computation, making it suitable for a large number of long viral genomic sequences.

Computational Analysis of Therapeutic Enzyme Uricase from Different Source Organisms

2020 ◽  
Vol 17 (1) ◽  
pp. 59-77
Author(s):  
Anand Kumar Nelapati ◽  
JagadeeshBabu PonnanEttiyappan
Keyword(s):  
Uric Acid ◽  
Amino Acid ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Protein Sequences ◽  
Amino Acid Sequences ◽  
Amino Acid Residues ◽  
Multiple Sequence ◽  
Physiochemical Properties ◽  
Pharmaceutical Industries

Background:Hyperuricemia and gout are the conditions, which is a response of accumulation of uric acid in the blood and urine. Uric acid is the product of purine metabolic pathway in humans. Uricase is a therapeutic enzyme that can enzymatically reduces the concentration of uric acid in serum and urine into more a soluble allantoin. Uricases are widely available in several sources like bacteria, fungi, yeast, plants and animals.Objective:The present study is aimed at elucidating the structure and physiochemical properties of uricase by insilico analysis.Methods:A total number of sixty amino acid sequences of uricase belongs to different sources were obtained from NCBI and different analysis like Multiple Sequence Alignment (MSA), homology search, phylogenetic relation, motif search, domain architecture and physiochemical properties including pI, EC, Ai, Ii, and were performed.Results:Multiple sequence alignment of all the selected protein sequences has exhibited distinct difference between bacterial, fungal, plant and animal sources based on the position-specific existence of conserved amino acid residues. The maximum homology of all the selected protein sequences is between 51-388. In singular category, homology is between 16-337 for bacterial uricase, 14-339 for fungal uricase, 12-317 for plants uricase, and 37-361 for animals uricase. The phylogenetic tree constructed based on the amino acid sequences disclosed clusters indicating that uricase is from different source. The physiochemical features revealed that the uricase amino acid residues are in between 300- 338 with a molecular weight as 33-39kDa and theoretical pI ranging from 4.95-8.88. The amino acid composition results showed that valine amino acid has a high average frequency of 8.79 percentage compared to different amino acids in all analyzed species.Conclusion:In the area of bioinformatics field, this work might be informative and a stepping-stone to other researchers to get an idea about the physicochemical features, evolutionary history and structural motifs of uricase that can be widely used in biotechnological and pharmaceutical industries. Therefore, the proposed in silico analysis can be considered for protein engineering work, as well as for gout therapy.

scholarly journals Analysis of Neurotoxin Cluster Genes in Clostridium botulinum Strains Producing Botulinum Neurotoxin Serotype A Subtypes

2008 ◽  
Vol 74 (9) ◽  
pp. 2778-2786 ◽  
Author(s):  
Mark J. Jacobson ◽  
Guangyun Lin ◽  
Brian Raphael ◽  
Joanne Andreadis ◽  
Eric A. Johnson
Keyword(s):  
Amino Acid ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Amino Acid Sequences ◽  
Gene Sequences ◽  
Amino Acid Levels ◽  
Cluster Type ◽  
Botulinum Neurotoxin Serotype A ◽  
Cluster Gene ◽  
Degree Of Similarity

ABSTRACT Neurotoxin cluster gene sequences and arrangements were elucidated for strains of Clostridium botulinum encoding botulinum neurotoxin (BoNT) subtypes A3, A4, and a unique A1-producing strain (HA− Orfx+ A1). These sequences were compared to the known neurotoxin cluster sequences of C. botulinum strains that produce BoNT/A1 and BoNT/A2 and possess either a hemagglutinin (HA) or an Orfx cluster, respectively. The A3 and HA− Orfx+ A1 strains demonstrated a neurotoxin cluster arrangement similar to that found in A2. The A4 strain analyzed possessed two sets of neurotoxin clusters that were similar to what has been found in the A(B) strains: an HA cluster associated with the BoNT/B gene and an Orfx cluster associated with the BoNT/A4 gene. The nucleotide and amino acid sequences of the neurotoxin cluster-specific genes were determined for each neurotoxin cluster and compared among strains. Additionally, the ntnh gene of each strain was compared on both the nucleotide and amino acid levels. The degree of similarity of the sequences of the ntnh genes and corresponding amino acid sequences correlated with the neurotoxin cluster type to which the ntnh gene was assigned.

scholarly journals Molecular characterization and phylogenetic analysis of NBS-LRR genes in wild relatives of eggplant (Solanum melongena L

2018 ◽  
Author(s):  
Sona. S Dev ◽  
P. Poornima ◽  
Akhil Venu
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Sequence Similarity ◽  
Interleukin 1 ◽  
Preliminary Investigation ◽  
Solanum Melongena ◽  
Wild Relatives ◽  
Amino Acid Sequences ◽  
R Genes ◽  
Multiple Sequence

Eggplantor brinjal (Solanum melongena L.), is highly susceptible to various soil-borne diseases. The extensive use of chemical fungicides to combat these diseases can be minimized by identification of resistance gene analogs (RGAs) in wild species of cultivated plants.In the present study, degenerate PCR primers for the conserved regions ofnucleotide binding site-leucine rich repeat (NBS-LRR) were used to amplify RGAs from wild relatives of eggplant (Black nightshade (Solanum nigrum), Indian nightshade (Solanumviolaceum)and Solanu mincanum) which showed resistance to the bacterial wilt pathogen, Ralstonia solanacearumin the preliminary investigation. The amino acid sequence of the amplicons when compared to each other and to the amino acid sequences of known RGAs deposited in Gen Bank revealed significant sequence similarity. The phylogenetic analysis indicated that they belonged to the toll interleukin-1 receptors (TIR)-NBS-LRR type R-genes. Multiple sequence alignment with other known R genes showed significant homology with P-loop, Kinase 2 and GLPL domains of NBS-LRR class genes. There has been no report on R genes from these wild eggplants and hence the diversity analysis of these novel RGAs can lead to the identification of other novel R genes within the germplasm of different brinjal plants as well as other species of Solanum.

Isolation and characterization of some novel genes of the apolipoprotein A-I family in Japanese eel, Anguilla japonica

2011 ◽  
Vol 6 (4) ◽  
pp. 545-557 ◽  
Author(s):  
Malay Choudhury ◽  
Takahiro Oku ◽  
Shoji Yamada ◽  
Masaharu Komatsu ◽  
Keita Kudoh ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Consensus Sequence ◽  
Structural Features ◽  
Lipid Binding ◽  
Japanese Eel ◽  
Amino Acid Sequences ◽  
Novel Genes ◽  
Isolation And Characterization

AbstractApolipoproteins such as apolipoprotein (apo) A-I, apoA-IV, and apoE are lipid binding proteins synthesized mainly in the liver and the intestine and play an important role in the transfer of exogenous or endogenous lipids through the circulatory system. To investigate the mechanism of lipid transport in fish, we have isolated some novel genes of the apoA-I family, apoIA-I (apoA-I isoform) 1–11, from Japanese eel by PCR amplification. Some of the isolated genes of apoIA-I corresponded to 28kDa-1 cDNAs which had already been deposited into the database and encoded an apolipoprotein with molecular weight of 28 kDa in the LDL, whereas others seemed to be novel genes. The structural organization of all apoIA-Is consisted of four exons separated by three introns. ApoIA-I10 had a total length of 3232 bp, whereas other genes except for apoIA-I9 ranged from 1280 to 1441 bp. The sequences of apoIA-Is at the exon-intron junctions were mostly consistent with the consensus sequence (GT/AG) at exon-intron boundaries, whereas the sequences of 3′ splice acceptor in intron 1 of apoIA-I1-7 were (AC) but not (AG). The deduced amino acid sequences of all apoIA-Is contained a putative signal peptide and a propeptide of 17 and 5 amino acid residues, respectively. The mature proteins of apoIA-I1-3, 7, and 8 consisted of 237 amino acids, whereas those of apoIA-I4-6 consisted of 239 amino acids. The mature apoIA-I10 sequence showed 65% identity to amino acid sequence of apoIA-I11 which was associated with an apolipoprotein with molecular weight of 23 kDa in the VLDL. All these mature apoIA-I sequences satisfied the common structural features depicted for the exchangeable apolipoproteins such as apoA-I, apoA-IV, and apoE but apoIA-I11 lacked internal repeats 7, 8, and 9 when compared with other members of apoA-I family. Phylogenetic analysis showed that these novel apoIA-Is isolated from Japanese eel were much closer to apoA-I than apoA-IV and apoE, suggesting new members of the apoA-I family.

scholarly journals Insertions and deletions trigger adaptive walks in Drosophila proteins

2012 ◽  
Vol 279 (1740) ◽  
pp. 3075-3082 ◽  
Author(s):  
Evgeny V. Leushkin ◽  
Georgii A. Bazykin ◽  
Alexey S. Kondrashov
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Molecular Adaptation ◽  
Amino Acid Substitutions ◽  
Protein Coding ◽  
Evolution Of Life ◽  
High Fraction ◽  
Adaptive Walks ◽  
The Difference ◽  
Almost All

Maps that relate all possible genotypes or phenotypes to fitness—fitness landscapes—are central to the evolution of life, but remain poorly known. An insertion or a deletion (indel) of one or several amino acids constitutes a substantial leap of a protein within the space of amino acid sequences, and it is unlikely that after such a leap the new sequence corresponds precisely to a fitness peak. Thus, one can expect an indel in the protein-coding sequence that gets fixed in a population to be followed by some number of adaptive amino acid substitutions, which move the new sequence towards a nearby fitness peak. Here, we study substitutions that occur after a frame-preserving indel in evolving proteins of Drosophila . An insertion triggers 1.03 ± 0.75 amino acid substitutions within the protein region centred at the site of insertion, and a deletion triggers 4.77 ± 1.03 substitutions within such a region. The difference between these values is probably owing to a higher fraction of effectively neutral insertions. Almost all of the triggered amino acid substitutions can be attributed to positive selection, and most of them occur relatively soon after the triggering indel and take place upstream of its site. A high fraction of substitutions that follow an indel occur at previously conserved sites, suggesting that an indel substantially changes selection that shapes the protein region around it. Thus, an indel is often followed by an adaptive walk of length that is in agreement with the theory of molecular adaptation.

scholarly journals Identification of amino acid sequences determining interaction between the cucumber mosaic virus-encoded 2a polymerase and 3a movement proteins

2007 ◽  
Vol 88 (12) ◽  
pp. 3445-3451 ◽  
Author(s):  
Min Sook Hwang ◽  
Kyung Nam Kim ◽  
Jeong Hyun Lee ◽  
Young In Park
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Critical Role ◽  
Amino Acid Sequences ◽  
Multiple Sequence ◽  
Movement Proteins ◽  
Gdd Motif

The cucumber mosaic virus (CMV)-encoded 3a movement protein (MP) is indispensable for CMV movement in plants. We have previously shown that MP interacts directly with the CMV-encoded 2a polymerase protein in vitro. Here, we further dissected this interaction and determined the amino acid sequences that are responsible for the MP and 2a polymerase protein interaction. Both the N-terminal 21 amino acids and the central GDD motif of the 2a polymerase protein were important for interacting with the MP. Although each of the regions alone was sufficient for the interaction with MP, quantitative yeast two-hybrid analyses showed that they acted synergistically to enhance the binding affinity. The MP N-terminal 20 amino acids were sufficient for interacting with the 2a polymerase protein, and the serine residue at position 14 played a critical role in the interaction. Multiple sequence alignment showed that the 2a protein interacting regions and the serine at position 14 in the MP are highly conserved among subgroup I and II CMV isolates.

scholarly journals Investigation of Two Evolutionarily Unrelated Halocarboxylic Acid Dehalogenase Gene Families

1999 ◽  
Vol 181 (8) ◽  
pp. 2535-2547 ◽  
Author(s):  
Katja E. Hill ◽  
Julian R. Marchesi ◽  
Andrew J. Weightman
Keyword(s):  
Amino Acid ◽  
Molecular Analysis ◽  
Phylogenetic Trees ◽  
Gene Families ◽  
Amino Acid Sequences ◽  
Group I ◽  
Silent Genes ◽  
Degrading Bacteria ◽  
Group Ii ◽  
Almost All

ABSTRACT Dehalogenases are key enzymes in the metabolism of halo-organic compounds. This paper describes a systematic approach to the isolation and molecular analysis of two families of bacterial α-halocarboxylic acid (αHA) dehalogenase genes, called group I and group II deh genes. The two families are evolutionarily unrelated and together represent almost all of the αHAdeh genes described to date. We report the design and evaluation of degenerate PCR primer pairs for the separate amplification and isolation of group I and II dehgenes. Amino acid sequences derived from 10 of 11 group Ideh partial gene products of new and previously reported bacterial isolates showed conservation of five residues previously identified as essential for activity. The exception, DehD from a Rhizobium sp., had only two of these five residues. Group II deh gene sequences were amplified from 54 newly isolated strains, and seven of these sequences were cloned and fully characterized. Group II dehalogenases were stereoselective, dechlorinating l- but not d-2-chloropropionic acid, and derived amino acid sequences for all of the genes exceptdehII°P11 showed conservation of previously identified essential residues. Molecular analysis of the twodeh families highlighted four subdivisions in each, which were supported by high bootstrap values in phylogenetic trees and by enzyme structure-function considerations. Group Ideh genes included two putative cryptic or silent genes, dehI°PP3 anddehI°17a, produced by different organisms. Group II deh genes included two cryptic genes and an active gene, dehII PP3, that can be switched off and on. All αHA-degrading bacteria so far described were Proteobacteria, a result that may be explained by limitations either in the host range fordeh genes or in isolation methods.

Phylogenetic and topological analyses of the bovine interferon-induced transmembrane protein (IFITM3)

2021 ◽  
Author(s):  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Multiple Sequence Alignment ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Phylogenetic Analyses ◽  
Amino Acid Sequences ◽  
Multiple Sequence ◽  
Interspecific Differences ◽  
Distinct Features

AbstractInterferon-induced transmembrane protein 3 (IFITM3) plays a pivotal role in antiviral capacity in several species. However, to date, investigations of the IFITM3 protein in cattle have been rare. According to recent studies, interspecific differences in the IFITM3 protein result in several unique features of the IFITM3 protein relative to primates and birds. Thus, in the present study, we investigated the bovine IFITM3 protein based on nucleotide and amino acid sequences to find its distinct features. We found that the bovine IFITM3 gene showed a significantly different length and homology relative to other species, including primates, rodents and birds. Phylogenetic analyses indicated that the bovine IFITM3 gene and IFITM3 protein showed closer evolutionary distance with primates than with rodents. However, cattle showed an independent clade among primates, rodents and birds. Multiple sequence alignment of the IFITM3 protein indicated that the bovine IFITM3 protein contains 36 bovine-specific amino acids. Notably, the bovine IFITM3 protein was predicted to prefer inside-to-outside topology of intramembrane domain 1 (IMD1) and inside-to-outside topology of transmembrane domain 2 by TMpred and three membrane embedding domains according to the SOSUI system.

scholarly journals Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering

2003 ◽  
Vol 372 (3) ◽  
pp. 725-734 ◽  
Author(s):  
Juan J. CALVETE ◽  
M. Paz MORENO-MURCIANO ◽  
R. David G. THEAKSTON ◽  
Dariusz G. KISIEL ◽  
Cezary MARCINKIEWICZ
Keyword(s):  
Amino Acid ◽  
K562 Cells ◽  
Amino Acid Sequences ◽  
Disulphide Bond ◽  
Vascular Cell Adhesion ◽  
Integrin Α5β1 ◽  
Multiple Sequence ◽  
Vipera Lebetina ◽  
Cell Adhesion Molecule 1 ◽  
Structural Diversification

We report the isolation and amino acid sequences of six novel dimeric disintegrins from the venoms of Vipera lebetina obtusa (VLO), V. berus (VB), V. ammodytes (VA), Echis ocellatus (EO) and Echis multisquamatus (EMS). Disintegrins VLO4, VB7, VA6 and EO4 displayed the RGD motif and inhibited the adhesion of K562 cells, expressing the integrin α5β1 to immobilized fibronectin. A second group of dimeric disintegrins (VLO5 and EO5) had MLD and VGD motifs in their subunits and blocked the adhesion of the α4β1 integrin to vascular cell adhesion molecule 1 with high selectivity. On the other hand, disintegrin EMS11 inhibited both α5β1 and α4β1 integrins with almost the same degree of specificity. Comparison of the amino acid sequences of the dimeric disintegrins with those of other disintegrins by multiple-sequence alignment and phylogenetic analysis, in conjunction with current biochemical and genetic data, supports the view that the different disintegrin subfamilies evolved from a common ADAM (adisintegrin and metalloproteinase-like) scaffold and that structural diversification occurred through disulphide bond engineering.

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