scholarly journals Изучение in silico структурных особенностей липаз из различных продуцентов как потенциальных агентов для иммобилизации на заряженных и гидрофобных носителях

2021 ◽  
Vol 21 (4) ◽  
pp. 555-567
Author(s):  
Даниил Юрьевич Богомолов ◽  
Фархат Адильжанович Сакибаев ◽  
Марина Геннадьевна Холявка ◽  
Валерий Григорьевич Артюхов ◽  
Владимир Федорович Селеменев
Keyword(s):  
In Silico ◽  
Burkholderia Cepacia ◽  
Homo Sapiens ◽  
Rhizomucor Miehei ◽  
Equus Caballus ◽  
Rhizopus Niveus

Липаза – гидролитический фермент, получаемый из многих организмов, таких как животные, растения, грибы и бактерии. Она осуществляет расщепление триглицеридов до моноглицеридов и жирных кислот, при этом обладает широкой субстратной специфичностью. Липазы применяются в пищевой промышленности и других сферах человеческой деятельности. Характерная особенность многих липаз – явление поверхностной активации, обуславливающее свойственную им зависимость скорости каталитической реакции от концентрации и агрегатного состояния субстрата. Доказано, что функционирование ферментов зависит от их структурных особенностей. Внутренние полости, туннели и поры являются неотъемлемыми компонентами нативной конформации белка. Они играют важную роль в транспорте субстрата, кофакторов и ионов к активному и регуляторным центрам фермента. Кроме того, их конфигурация может влиять на термостабильность энзимов, в связи с чем изучение вышеперечисленных структур является необходимым для понимания механизмов функционирования биокатализаторов. Также важным элементом структуры ферментов являются скопления заряженных и гидрофобных аминокислотных остатков на их поверхности. Данное свойство необходимо учитывать при планировании путей адсорбционной иммобилизации биокатализаторов на различных носителях для использования в промышленности и медицине. В работе исследованы состав, локализация и конфигурация внутренних полостей, туннелей, пор, а также поверхностных скоплений заряженных и гидрофобных аминокислотных остатков в молекулах липаз из Rhizopus niveus (PDB ID: 1LGY), Rhizomucor miehei (PDB ID: 3TGL), Burkholderia cepacia (PDB ID: 1OIL), панкреатических липаз Homo sapiens (PDB ID: 1N8S) и Equus caballus (PDB ID: 1HPL). Для расчета параметров и визуализации данных структур использовались программы MOLE и Maestro. Показано наличие соответственно 2, 1, 5, 5 и 2 туннелей и отсутствие пор для данных ферментов; а также наличие по 6 внутренних полостей для липаз из R. niveus и E. caballus, 5 внутренних полостей для молекулы из R. miehei и по 2 внутренних полости для энзимов из B. cepacia и H. sapiens. Приведены аминокислотный состав и профили туннелей изучаемых липаз. Выявлено, что данные структуры не сообщаются друг с другом общими пустотами. Установлено преобладание гидрофобных аминокислотных остатков в большинстве туннелей данных ферментов. Изучены структура, локализация и состав скоплений заряженных и гидрофобных аминокислотных остатков на поверхностях макромолекул. Выявлено возможное влияние расположения данных скоплений на связывание липаз с носителем при их адсорбционной иммобилизации.

scholarly journals Upgrading of Farmed Salmon Oil Through Lipase-Catalyzed Hydrolysis

2010 ◽  
Vol 4 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Derya Kahveci ◽  
Mia Falkeborg ◽  
Sandra Gregersen ◽  
Xuebing Xu
Keyword(s):  
Burkholderia Cepacia ◽  
Rhizopus Oryzae ◽  
Candida Rugosa ◽  
Rhizomucor Miehei ◽  
Omega 3 ◽  
Pufa Content ◽  
Reaction Conditions ◽  
Farmed Salmon ◽  
Rhizopus Niveus ◽  
The Relationship

Upgrading of farmed salmon oil obtained from by-products was carried out by lipase-catalyzed hydrolysis to increase omega 3 polyunsaturated fatty acids (PUFA) content. The lipases tested were from Penicillium camembertii (PC), Rhizomucor javanicus (RJ), Rhizopus niveus (RN), Rhizopus delemar (RD), Burkholderia cepacia (BC), Rhizopus oryzae (RO), Candida rugosa (CR) and Rhizomucor miehei (RM). The lipases from PC, RJ and RN had lower hydrolysis degrees (HDs) compared to the rest of the lipases. The lipase from CR had the highest HD after 24 h (91.89%). Moreover, CR lipase was the most effective one in concentrating omega 3 PUFA. The final value was increased from 13.77% to 27.81% (wt%). The changes in omega 3 PUFA content were significantly different among the lipases although the HD values were similar at the end of the reactions, which was believed to be caused by the substrate specificities of the lipases. The investigation of the relationship between HD and hydrolysis resistant value (HRV) for eicosapentaenoic acid (EPA, 20:5), docosahexaenoic acid (DHA, 22:6) and oleic acid (OA, 18:1) revealed that the fatty acid (FA) selectivity of the lipases were significantly different. CR lipase had the highest preference for hydrolyzing OA selectively over EPA and DHA. The reaction conditions, i.e. presence of surfactants, sonication, buffer-to-oil ratio, enzyme load, did not affect the selectivity. Investigation of the reaction conditions revealed that it was possible to obtain ~2.15-fold of the original omega 3 PUFA content by hydrolysis of salmon oil in the presence of CR lipase (4%, based on oil weight) with a bufferto- oil ratio of 2:1 (v/v) at 37oC for 4 h.

scholarly journals IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

2020 ◽  
Author(s):  
Oladoja AWofisayo
Keyword(s):  
Comparative Genomics ◽  
Peer Review ◽  
In Silico ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Mammalian Species ◽  
Target Selection ◽  
Plasmodium Species ◽  
Data Bank ◽  
Sequence Motifs

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

Potential Drug Target Identification in Porphyromonas gingivalis using In-silico Subtractive Metabolic Pathway Analysis

2021 ◽  
Vol 20 (4) ◽  
pp. 887-896
Author(s):  
Prachi Sao ◽  
Yamini Chand ◽  
Atul Kumar ◽  
Sachidanand Singh
Keyword(s):  
Porphyromonas Gingivalis ◽  
Pathway Analysis ◽  
In Silico ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Medical Science ◽  
Bone Destruction ◽  
Therapeutic Drug ◽  
Potential Drug ◽  
Narrow Spectrum

Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear. Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrugresistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens. Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis. Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets. Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection. Bangladesh Journal of Medical Science Vol.20(4) 2021 p.887-896

Genes to drug: an in-silico approach to design a drug for Huntington disease (HD) in Homo sapiens

2021 ◽  
Vol 14 (3) ◽  
pp. 190
Author(s):  
Manoj Kumar Sharma ◽  
Manoj Kumar Sharma ◽  
Shivalika Panwar ◽  
Sachin Kumar
Keyword(s):  
Huntington Disease ◽  
In Silico ◽  
Homo Sapiens

Genes to drug: an in-silico approach to design a drug for Huntington disease (HD) in Homo sapiens

2021 ◽  
Vol 14 (3) ◽  
pp. 190
Author(s):  
Sachin Kumar ◽  
Shivalika Panwar ◽  
Manoj Kumar Sharma ◽  
Manoj Kumar Sharma
Keyword(s):  
Huntington Disease ◽  
In Silico ◽  
Homo Sapiens

IN SILICO CHARACTERIZATION AND MOLECULAR MODELLING OF SODIUM-DEPENDENT SEROTONIN TRANSPORTER PROTEIN FROM HOMO SAPIENS

2017 ◽  
Vol 10 (8) ◽  
pp. 299
Author(s):  
Hina Bansal ◽  
Neetu Jabalia
Keyword(s):  
Homology Modeling ◽  
Serotonin Transporter ◽  
In Silico ◽  
Tertiary Structure ◽  
Homo Sapiens ◽  
Receptor Protein ◽  
Sudden Infant ◽  
Protein Disorder ◽  
Computational Tools ◽  
Sodium Dependent

Objective: The objective of our investigation is to apply computational tools for a protein sodium-dependent serotonin transporter (SERT). It plays a role in sudden infant death syndrome, aggressive behavior in Alzheimer disease, and depression-susceptibility. Although various conventional and experimental therapies have been directed for the treatment, still it needs attention for more effective treatments. Toward this pursuit, we performed in silico analysis of the protein using computational tools and servers.Methods: Homology modeling approach has been used to define the tertiary structure of the protein using SWISS-MODEL workspace. Modal validation was done to verify the generated modal. Furthermore, primary and secondary structural and functional analysis was performed to provide more perceptions into the selected protein. The protein disorder analysis was performed using PrDOS server.Results: The results of the primary structure analyses suggested that SERT is an acidic and hydrophobic protein in nature. It is structurally stable. The secondary structural analysis results revealed that random coils dominated among secondary structure elements. The homology modeling showed that the QMEAN score of the model was −5.17, and the sequence identity was 52%. Validation protein models using Rampage revealed that more that 95.9% residues were in favored regions. The protein disorder detected by PrDOS showed the total disorder amino acid residues were 89 (14.1%).Conclusion: The study provides valuable clues for initiation of experimental characterization of this protein and throws light on some novel insights into the structural features of sodium-dependent SERT protein from Homo sapiens. This will also helpful in conducting docking studies for the receptor protein against various drug molecules. 

scholarly journals Mycobacterium tuberculosis H37Rv: In Silico Drug Targets Identification by Metabolic Pathways Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Asad Amir ◽  
Khyati Rana ◽  
Arvind Arya ◽  
Neelesh Kapoor ◽  
Hirdesh Kumar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
In Silico ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Homo Sapiens ◽  
Protein Sequences ◽  
Mycobacterium Tuberculosis H37rv ◽  
Drug Molecules ◽  
Pathways Analysis

Mycobacterium tuberculosis (Mtb) is a pathogenic bacteria species in the genus Mycobacterium and the causative agent of most cases of tuberculosis. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. This antibiotic resistance strain lead to development of the new antibiotics or drug molecules which can kill or suppress the growth of Mycobacterium tuberculosis. We have performed an in silico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen Mycobacterium tuberculosis (H37Rv). Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to M. tuberculosis. We have identified five unique pathways for Mycobacterium tuberculosis having a number of 60 enzymes, which are nonhomologous to Homo sapiens protein sequences, and among them there were 55 enzymes, which are nonhomologous to Homo sapiens protein sequences. These enzymes were also found to be essential for survival of the Mycobacterium tuberculosis according to the DEG database. Further, the functional analysis using Uniprot showed involvement of all the unique enzymes in the different cellular components.

scholarly journals In silico comparative analysis of BRCA2 gene in some selected animal species in Africa

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Olotu TM ◽  
Oladipo EK ◽  
Ajibade OA ◽  
Adeosun I. J ◽  
Adegunloye DV ◽  
...  
Keyword(s):  
In Silico ◽  
Animal Species ◽  
Homo Sapiens ◽  
Cell Structure ◽  
Bird Species ◽  
Brca2 Gene ◽  
African Region ◽  
African Countries ◽  
Multiple Sequence ◽  
Theropithecus Gelada

Background: BRCA2 genes are not only found in humans, but in other animal species. BRCA2 gene plays a vital role in maintaining the stability of a cell's genetic information. BRCA2 is considered as a gatekeeper gene; however, if mutated or abnormally expressed, it causes the destruction of normal cell structure and promotes the growth of cancer cells. Objective: This study aimed to assess the differences and similarities of BRCA2 gene from different animal species in Africa through In silico genomics analysis providing further insight on its comparative genomics features. Materials and Methods: Fifteen nucleotide sequences of BRCA2 gene of different mammals and bird species were retrieved from National Centre for Biotechnology Information (NCBI). Multiple sequence alignment was done with MEGA 7.0 software, while identity and similarities were determined by constructing a pairwise comparison. Conserved domains on the sequences were identified with NCB1-CDD. Results: BRCA2 gene was found to be present not only in humans, but other lower animals and birds across African countries. The phylogenetic tree for Homo sapiens BRCA2 gene in Tunisia belongs to the same ecological niche with the Theropithecus gelada BRCA2 gene in Ethiopia and BRCA2 from the same African region has high bootstrap, implying that they share the same homology. Conserved regions identified in the all the sequences were absent in Miniopterus natalensis and most present in Chrysochloris asiatica, Theropithecus gelada, Apaloderma vittatum, Pterocles gutturalis, Rousettus aegyptiacus, Homo sapiens, Echinops telfairi, and Cavia porcellus. Conclusion: Based on the findings obtained from this study, BRCA2 gene in humans and other lower animals, particularly from same region, share the same homology and similarities.

scholarly journals In Silico Analysis of Fungal and Chloride-Dependent α-Amylases within the Family GH13 with Identification of Possible Secondary Surface-Binding Sites

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5704
Author(s):  
Zuzana Janíčková ◽  
Štefan Janeček
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Homo Sapiens ◽  
In Silico Analysis ◽  
Surface Binding ◽  
Conserved Sequence ◽  
Evolutionary Relatedness ◽  
The Family ◽  
Tim Barrel ◽  
Silico Analysis

This study brings a detailed bioinformatics analysis of fungal and chloride-dependent α-amylases from the family GH13. Overall, 268 α-amylase sequences were retrieved from subfamilies GH13_1 (39 sequences), GH13_5 (35 sequences), GH13_15 (28 sequences), GH13_24 (23 sequences), GH13_32 (140 sequences) and GH13_42 (3 sequences). Eight conserved sequence regions (CSRs) characteristic for the family GH13 were identified in all sequences and respective sequence logos were analysed in an effort to identify unique sequence features of each subfamily. The main emphasis was given on the subfamily GH13_32 since it contains both fungal α-amylases and their bacterial chloride-activated counterparts. In addition to in silico analysis focused on eventual ability to bind the chloride anion, the property typical mainly for animal α-amylases from subfamilies GH13_15 and GH13_24, attention has been paid also to the potential presence of the so-called secondary surface-binding sites (SBSs) identified in complexed crystal structures of some particular α-amylases from the studied subfamilies. As template enzymes with already experimentally determined SBSs, the α-amylases from Aspergillus niger (GH13_1), Bacillus halmapalus, Bacillus paralicheniformis and Halothermothrix orenii (all from GH13_5) and Homo sapiens (saliva; GH13_24) were used. Evolutionary relationships between GH13 fungal and chloride-dependent α-amylases were demonstrated by two evolutionary trees—one based on the alignment of the segment of sequences spanning almost the entire catalytic TIM-barrel domain and the other one based on the alignment of eight extracted CSRs. Although both trees demonstrated similar results in terms of a closer evolutionary relatedness of subfamilies GH13_1 with GH13_42 including in a wider sense also the subfamily GH13_5 as well as for subfamilies GH13_32, GH13_15 and GH13_24, some subtle differences in clustering of particular α-amylases may nevertheless be observed.

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