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Fulltext Genome analysis of quorum sensing Cedecea neteri SSMD04 leads to identification of its novel signaling synthase (cneI), cognate receptor (cneR) and an orphan receptor

Tan KH, Tan JY, Yin WF, Chan KG

PeerJ, 2015;3:e1216.
PMID: 26355540 DOI: 10.7717/peerj.1216

Cedecea neteri is a very rare human pathogen. We have isolated a strain of C. neteri SSMD04 from pickled mackerel sashimi identified using molecular and phenotypics approaches. Using the biosensor Chromobacterium violaceum CV026, we have demonstrated the presence of short chain N-acyl-homoserine lactone (AHL) type quorum sensing (QS) activity in C. neteri SSMD04. Triple quadrupole LC/MS analysis revealed that C. neteri SSMD04 produced short chain N-butyryl-homoserine lactone (C4-HSL). With the available genome information of C. neteri SSMD04, we went on to analyse and identified a pair of luxI/R homologues in this genome that share the highest similarity with croI/R homologues from Citrobacter rodentium. The AHL synthase, which we named cneI(636 bp), was found in the genome sequences of C. neteri SSMD04. At a distance of 8bp from cneI is a sequence encoding a hypothetical protein, potentially the cognate receptor, a luxR homologue which we named it as cneR. Analysis of this protein amino acid sequence reveals two signature domains, the autoinducer-binding domain and the C-terminal effector which is typical characteristic of luxR. In addition, we found that this genome harboured an orphan luxR that is most closely related to easR in Enterobacter asburiae. To our knowledge, this is the first report on the AHL production activity in C. neteri, and the discovery of its luxI/R homologues, the orphan receptor and its whole genome sequence.

Matched MeSH terms: Amino Acid Sequence
Nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of a Malaysian heat resistant viscerotropic-velogenic Newcastle disease virus (NDV) strain AF2240

Tan WS, Lau CH, Ng BK, Ibrahim AL, Yusoff K

DNA Seq., 1995;6(1):47-50.
PMID: 8746461

The nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of Newcastle disease virus (NDV) viscerotropic-velogenic strain AF2240 was determined by direct RNA sequencing and by sequencing RT-PCR products. It encodes a single open reading frame of 581 amino acids with a calculated Mr of 63.8 kDa. The predicted sequence contains five asparagine glycosylation sites. Comparison of the AF2240 HN protein sequence with 13 other previously published sequences showed 88% homology. This HN protein is unique because it lacked the Arg 403 residue which is present in all of the other strains and cannot be grouped under the proposed three size classes of HN proteins in NDV.

Matched MeSH terms: Amino Acid Sequence
Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease

Sharma JN, Buchanan WW

Exp. Toxicol. Pathol., 1994 Dec;46(6):421-33.
PMID: 7703672 DOI: 10.1016/S0940-2993(11)80053-9

Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.

Matched MeSH terms: Amino Acid Sequence
Bacillus sphaericus strain 2297: nucleotide sequence of 41.9 kDa toxin gene

Hindley J, Berry C

Nucleic Acids Res, 1988 May 11;16(9):4168.
PMID: 3375083
Matched MeSH terms: Amino Acid Sequence
Minireview: applied structural bioinformatics in proteomics

Choong YS, Tye GJ, Lim TS

Protein J, 2013 Oct;32(7):505-11.
PMID: 24096348 DOI: 10.1007/s10930-013-9514-1

The limited sequence similarity of protein sequences with known structures has led to an indispensable need for computational technology to predict their structures. Structural bioinformatics (SB) has become integral in elucidating the sequence-structure-function relationship of a protein. This report focuses on the applications of SB within the context of protein engineering including its limitation and future challenges.

Matched MeSH terms: Amino Acid Sequence
Protein replenishment in pitcher fluids of Nepenthes × ventrata revealed by quantitative proteomics (SWATH-MS) informed by transcriptomics

Wan Zakaria WNA, Aizat WM, Goh HH, Mohd Noor N

J Plant Res, 2019 Sep;132(5):681-694.
PMID: 31422552 DOI: 10.1007/s10265-019-01130-w

Carnivorous plants capture and digest insects for nutrients, allowing them to survive in soil deprived of nitrogenous nutrients. Plants from the genus Nepenthes produce unique pitchers containing secretory glands, which secrete enzymes into the digestive fluid. We performed RNA-seq analysis on the pitcher tissues and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis on the pitcher fluids of Nepenthes × ventrata to study protein expression in this carnivory organ during early days of pitcher opening. This transcriptome provides a sequence database for pitcher fluid protein identification. A total of 32 proteins of diverse functions were successfully identified in which 19 proteins can be quantified based on label-free quantitative proteomics (SWATH-MS) analysis while 16 proteins were not reported previously. Our findings show that certain proteins in the pitcher fluid were continuously secreted or replenished after pitcher opening, even without any prey or chitin induction. We also discovered a new aspartic proteinase, Nep6, secreted into pitcher fluid. This is the first SWATH-MS analysis of protein expression in Nepenthes pitcher fluid using a species-specific reference transcriptome. Taken together, our study using a gel-free shotgun proteomics informed by transcriptomics (PIT) approach showed the dynamics of endogenous protein secretion in the digestive organ of N. × ventrata and provides insights on protein regulation during early pitcher opening prior to prey capture.

Matched MeSH terms: Amino Acid Sequence
Fulltext Homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8

Garba L, Mohamad Yussoff MA, Abd Halim KB, Ishak SNH, Mohamad Ali MS, Oslan SN, et al.

PeerJ, 2018;6:e4347.
PMID: 29576935 DOI: 10.7717/peerj.4347

Membrane-bound fatty acid desaturases perform oxygenated desaturation reactions to insert double bonds within fatty acyl chains in regioselective and stereoselective manners. The Δ9-fatty acid desaturase strictly creates the first double bond between C9 and 10 positions of most saturated substrates. As the three-dimensional structures of the bacterial membrane fatty acid desaturases are not available, relevant information about the enzymes are derived from their amino acid sequences, site-directed mutagenesis and domain swapping in similar membrane-bound desaturases. The cold-tolerantPseudomonassp. AMS8 was found to produce high amount of monounsaturated fatty acids at low temperature. Subsequently, an active Δ9-fatty acid desaturase was isolated and functionally expressed inEscherichia coli. In this paper we report homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8 for the first time to the best of our knowledge. Three dimensional structure of the enzyme was built using MODELLER version 9.18 using a suitable template. The protein model contained the three conserved-histidine residues typical for all membrane-bound desaturase catalytic activity. The structure was subjected to energy minimization and checked for correctness using Ramachandran plots and ERRAT, which showed a good quality model of 91.6 and 65.0%, respectively. The protein model was used to preform MD simulation and docking of palmitic acid using CHARMM36 force field in GROMACS Version 5 and Autodock tool Version 4.2, respectively. The docking simulation with the lowest binding energy, -6.8 kcal/mol had a number of residues in close contact with the docked palmitic acid namely, Ile26, Tyr95, Val179, Gly180, Pro64, Glu203, His34, His206, His71, Arg182, Thr85, Lys98 and His177. Interestingly, among the binding residues are His34, His71 and His206 from the first, second, and third conserved histidine motif, respectively, which constitute the active site of the enzyme. The results obtained are in compliance with thein vivoactivity of the Δ9-fatty acid desaturase on the membrane phospholipids.

Matched MeSH terms: Amino Acid Sequence
Purification and N-terminal amino acid sequence of fructose-6-phosphate phosphoketolase from Bifidobacterium longum BB536

Fandi KG, Ghazali HM, Yazid AM, Raha AR

Lett Appl Microbiol, 2001 Apr;32(4):235-9.
PMID: 11298932

AIMS: The key enzyme in the fructose-6-phosphate shunt in bifidobacteria, Fructose-6-phosphate phosphoketolase (F6PPK; E.C. 4.1.2.22.), was purified to electrophoretic homogeneity for the first time from Bifidobacterium longum (BB536).
METHODS AND RESULTS: A three-step procedure comprising acetone fractionation followed by fast protein liquid chromatography (FPLC) resulted in a 30-fold purification. The purified enzyme had a molecular mass of 300 +/- 5 kDa as determined by gel filtration. It is probably a tetramer containing two different subunits with molecular masses of 93 +/- 1 kDa and 59 +/- 0.5 kDa, as determined by SDS-PAGE.
CONCLUSION: The deduced N-terminal amino acid sequences of the two subunits revealed no significant similarity between them and other proteins when compared to the data bases of EMBL and SWISS-PROT, indicating that this could be the first report on N-terminal amino acid sequence of F6PPK.
SIGNIFICANCE AND IMPACT OF THE STUDY: The data from this study will be used to design oligonucleotide probe specific for bifidobacteria and to study the gene encoded F6PPK.

Matched MeSH terms: Amino Acid Sequence
Fulltext In silico-based vaccine design against Ebola virus glycoprotein

Dash R, Das R, Junaid M, Akash MF, Islam A, Hosen SZ

Adv Appl Bioinform Chem, 2017;10:11-28.
PMID: 28356762 DOI: 10.2147/AABC.S115859

Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154-162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.

Matched MeSH terms: Amino Acid Sequence
Molecular Characterization of Avian Infectious Bronchitis Virus Isolated in Malaysia during 2014-2016

Leow BL, Syamsiah Aini S, Faizul Fikri MY, Muhammad Redzwan S, Khoo CK, Ong GH, et al.

Trop Biomed, 2018 Dec 01;35(4):1092-1106.
PMID: 33601856

Avian Infectious Bronchitis (IB) is a highly contagious disease which can cause huge economic losses to the poultry industry. Forty five IB viruses (IBV) were isolated from poultry in Malaysia during 2014-2016. Phylogenetic analysis of the spike glycoprotein 1 (S1) gene revealed that all isolates were clustered into five distinct groups. The predominant type of IBV isolated was QX strains (47%), second was 4/91 type (27%), followed by Malaysian strain MH5365/95 (13%), Massachusetts type (11%) and finally Taiwanese strains (2%). Four types of S1 protein cleavage recognition motifs were found among the isolates which includes HRRRR, RRSRR, RRFRR and RRVRR. To our knowledge, this is the first report describing the motif RRVRR and are unique to Malaysian strains. Six IBVs were grouped in Malaysian MH5365/95 strains. Among these, one isolate was different from others where it only shared 82% identity with MH5365/95 and to others. It formed its own branch in the Malaysian cluster suggesting it may be a variant unique to Malaysia. Alignment analysis of the S1 amino acid sequences indicated that point mutations, insertions and deletions contribute to the divergence of IB variants. This study indicated at least five groups of IBV are circulating in Malaysia with most of the isolates belonged to QX strains. As new IBV variants continue to emerge, further study need to be carried out to determine whether the current available vaccine is able to give protection against the circulating virus.

Matched MeSH terms: Amino Acid Sequence
Fulltext TG-SK, a teak (Tectona grandis Linn.) homolog of GSK-3/ shaggy protein kinase

Norlia B., Norwati M., Norwati A., Mohd Rosli H., Norihan M. S.

Buletin Persatuan Genetik Malaysia, 2006;12(1):7-8.
MyJurnal

This study was part of the larger studies to isolate and characterize gene related to flowering in teak. This study isolated differentially expressed genes of teak flowering tissues. One of the genes encodes plant protein kinases highly homologous to the AtSK-II of Arabidopsis GSK3/SHAGGY subfamily. The gene was named as Tectona grandis SHAGGY kinase (Tg-SK). The protein sequence of this gene contained the characteristic catalytic domain of GSK-3/SHAGGY protein kinase. The gene also shows the same genomic organization of 11 introns and 12 exons. Although the size of the introns varies, the positions of exon/intron boundaries are very similar to AtSK-II. The discovery of this gene in teak, which is a forest tree species, supports the hypothesis, which suggested the gene is found in all eukaryotes.

Matched MeSH terms: Amino Acid Sequence
Fulltext Isolation and molecular detection of Newcastle Disease virus from an imported meat sample

Leow, B.L., Syamsiah, A.S., Ong, G.H., Faizul, F.M.Y., Muhammad, R.S., Basirah, M.A., et al.

Jurnal Veterinar Malaysia, 2016;28(2):17-20.
MyJurnal

Infected poultry meat plays an important role in the spread of Newcastle Disease (ND). In this study, an imported meat product was found to be positive for ND by both virus isolation and molecular characterization. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that the isolate was virulent as indicated by the sequence 112RRQKR116 for the Cterminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. Basic Local Alignment Search Tool (BLAST) analysis showed the isolate was 98% identical with China Hebei ND strain. Though the regulations for the importation of poultry meat for human consumption into Malaysia are strict, the possibility of the persistence of ND virus in imported meat is prevalent. Strict enforcement of importing regulations and screening the disease in imported poultry meat is important to ensure food safety and prevent introducing ND strain fInfected poultry meat plays an important role in the spread of Newcastle Disease (ND). In this study, an imported meat product was found to be positive for ND by both virus isolation and molecular characterization. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that the isolate was virulent as indicated by the sequence 112RRQKR116 for the Cterminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. Basic Local Alignment Search Tool (BLAST) analysis showed the isolate was 98% identical with China Hebei ND strain. Though the regulations for the importation of poultry meat for human consumption into Malaysia are strict, the possibility of the persistence of ND virus in imported meat is prevalent. Strict enforcement of importing regulations and screening the disease in imported poultry meat is important to ensure food safety and prevent introducing ND strain from other countries into Malaysiarom other countries into Malaysia.

Matched MeSH terms: Amino Acid Sequence
Molecular Modeling and Simulation of Transketolase from Orthosiphon stamineus

Ng ML, Rahmat ZB, Bin Omar MSS

Curr Comput Aided Drug Des, 2019;15(4):308-317.
PMID: 30345923 DOI: 10.2174/1573409914666181022141753

BACKGROUND: Orthosiphon stamineus is a traditional medicinal plant in Southeast Asia countries with various well-known pharmacological activities such as antidiabetic, diuretics and antitumor activities. Transketolase is one of the proteins identified in the leaves of the plant and transketolase is believed able to lower blood sugar level in human through non-pancreatic mechanism. In order to understand the protein behavioral properties, 3D model of transketolase and analysis of protein structure are of obvious interest.
METHODS: In the present study, 3D model of transketolase was constructed and its atomic characteristics revealed. Besides, molecular dynamic simulation of the protein at 310 K and 368 K deciphered transketolase may be a thermophilic protein as the structure does not distort even at elevated temperature. This study also used the protein at 310 K and 368 K resimulated back at 310 K environment.
RESULTS: The results revealed that the protein is stable at all condition which suggest that it has high capacity to adapt at different environment not only at high temperature but also from high temperature condition to low temperature where the structure remains unchanged while retaining protein function.
CONCLUSION: The thermostability properties of transketolase is beneficial for pharmaceutical industries as most of the drug making processes are at high temperature condition.

Matched MeSH terms: Amino Acid Sequence
Comparative structural analysis of fruit and stem bromelain from Ananas comosus

Ramli ANM, Manas NHA, Hamid AAA, Hamid HA, Illias RM

Food Chem, 2018 Nov 15;266:183-191.
PMID: 30381175 DOI: 10.1016/j.foodchem.2018.05.125

Cysteine proteases in pineapple (Ananas comosus) plants are phytotherapeutical agents that demonstrate anti-edematous, anti-inflammatory, anti-thrombotic and fibrinolytic activities. Bromelain has been identified as an active component and as a major protease of A. comosus. Bromelain has gained wide acceptance and compliance as a phytotherapeutical drug. The proteolytic fraction of pineapple stem is termed stem bromelain, while the one presents in the fruit is known as fruit bromelain. The amino acid sequence and domain analysis of the fruit and stem bromelains demonstrated several differences and similarities of these cysteine protease family members. In addition, analysis of the modelled fruit (BAA21848) and stem (CAA08861) bromelains revealed the presence of unique properties of the predicted structures. Sequence analysis and structural prediction of stem and fruit bromelains of A. comosus along with the comparison of both structures provides a new insight on their distinct properties for industrial application.

Matched MeSH terms: Amino Acid Sequence
Fulltext Analysis of viral diversity for vaccine target discovery

Khan AM, Hu Y, Miotto O, Thevasagayam NM, Sukumaran R, Abd Raman HS, et al.

BMC Med Genomics, 2017 12 21;10(Suppl 4):78.
PMID: 29322922 DOI: 10.1186/s12920-017-0301-2

BACKGROUND: Viral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets.
RESULTS: This work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples. Our methodology has been implemented as an analytical pipeline that brings significant advancement to the field of reverse vaccinology, enabling systematic screening of known sequence data in nature for identification of vaccine targets. This includes key steps (i) comprehensive and extensive collection of sequence data of viral proteomes (the virome), (ii) data cleaning, (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra- and inter-species variation analysis of conserved sequences, including human homology analysis, and (vi) functional and immunological relevance analysis.
CONCLUSION: These steps are combined into the pipeline ensuring that a more refined process, as compared to a simple evolutionary conservation analysis, will facilitate a better selection of vaccine targets and their prioritization for subsequent experimental validation.

Matched MeSH terms: Amino Acid Sequence
Fulltext NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning

Høie MH, Kiehl EN, Petersen B, Nielsen M, Winther O, Nielsen H, et al.

Nucleic Acids Res, 2022 Jul 05;50(W1):W510-W515.
PMID: 35648435 DOI: 10.1093/nar/gkac439

Recent advances in machine learning and natural language processing have made it possible to profoundly advance our ability to accurately predict protein structures and their functions. While such improvements are significantly impacting the fields of biology and biotechnology at large, such methods have the downside of high demands in terms of computing power and runtime, hampering their applicability to large datasets. Here, we present NetSurfP-3.0, a tool for predicting solvent accessibility, secondary structure, structural disorder and backbone dihedral angles for each residue of an amino acid sequence. This NetSurfP update exploits recent advances in pre-trained protein language models to drastically improve the runtime of its predecessor by two orders of magnitude, while displaying similar prediction performance. We assessed the accuracy of NetSurfP-3.0 on several independent test datasets and found it to consistently produce state-of-the-art predictions for each of its output features, with a runtime that is up to to 600 times faster than the most commonly available methods performing the same tasks. The tool is freely available as a web server with a user-friendly interface to navigate the results, as well as a standalone downloadable package.

Matched MeSH terms: Amino Acid Sequence
Angiostrongylus mackerrasae and A. cantonensis (Nematoda: Metastrongyloidea) belong to same genetic lineage: evidence from mitochondrial protein-coding genes

Song SL, Yong HS, Eamsobhana P

J Helminthol, 2018 Jul;92(4):524-529.
PMID: 28693647 DOI: 10.1017/S0022149X1700061X

Angiostrongylus mackerrasae is a parasitic nematode of rats found in Australia. When first reported, it was referred to as A. cantonensis. Recent molecular studies, including the mitochondrial genome, indicate that it is highly similar to A. cantonensis. These studies did not include A. malaysiensis, another member of the A. cantonensis species complex, for comparison. The present study examined the genetic distance and phylogenetic relationship between the component taxa (A. cantonensis, A. mackerrasae and A. malaysiensis) of the A. cantonensis species complex, based on the 12 protein-coding genes (PCGs) of their mitochondrial genome. Both the nucleotide and amino acid sequences were analysed. Angiostrongylus mackerrasae and A. cantonensis are members of the same genetic lineage and both are genetically distinct from A. malaysiensis. The genetic distance based on concatenated nucleotide sequences of 12 mt-PCGs between A. mackerrasae and A. cantonensis from Thailand is p = 1.73%, while that between the Thai and Chinese taxa of A. cantonensis is p = 3.52%; the genetic distance between A. mackerrasae and A. cantonensis from China is p = 3.70%. The results indicate that A. mackerrasae and A. cantonensis belong to the same genetic lineage, and that A. mackerrasae may be conspecific with A. cantonensis. It remains to be resolved whether A. mackerrasae is conspecific with A. cantonensis or undergoing incipient speciation.

Matched MeSH terms: Amino Acid Sequence
Fulltext Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19

Faheem, Kumar BK, Sekhar KVGC, Kunjiappan S, Jamalis J, Balaña-Fouce R, et al.

Bioorg Chem, 2020 Nov;104:104269.
PMID: 32947136 DOI: 10.1016/j.bioorg.2020.104269

COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as Mpro) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, Mpro, endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.

Matched MeSH terms: Amino Acid Sequence
Fulltext Computational identification of 4-carboxyglutamate sites to supplement physiological studies using deep learning

Naseer S, Ali RF, Fati SM, Muneer A

Sci Rep, 2022 01 07;12(1):128.
PMID: 34996975 DOI: 10.1038/s41598-021-03895-4

In biological systems, Glutamic acid is a crucial amino acid which is used in protein biosynthesis. Carboxylation of glutamic acid is a significant post-translational modification which plays important role in blood coagulation by activating prothrombin to thrombin. Contrariwise, 4-carboxy-glutamate is also found to be involved in diseases including plaque atherosclerosis, osteoporosis, mineralized heart valves, bone resorption and serves as biomarker for onset of these diseases. Owing to the pathophysiological significance of 4-carboxyglutamate, its identification is important to better understand pathophysiological systems. The wet lab identification of prospective 4-carboxyglutamate sites is costly, laborious and time consuming due to inherent difficulties of in-vivo, ex-vivo and in vitro experiments. To supplement these experiments, we proposed, implemented, and evaluated a different approach to develop 4-carboxyglutamate site predictors using pseudo amino acid compositions (PseAAC) and deep neural networks (DNNs). Our approach does not require any feature extraction and employs deep neural networks to learn feature representation of peptide sequences and performing classification thereof. Proposed approach is validated using standard performance evaluation metrics. Among different deep neural networks, convolutional neural network-based predictor achieved best scores on independent dataset with accuracy of 94.7%, AuC score of 0.91 and F1-score of 0.874 which shows the promise of proposed approach. The iCarboxE-Deep server is deployed at https://share.streamlit.io/sheraz-n/carboxyglutamate/app.py .

Matched MeSH terms: Amino Acid Sequence
Fulltext General overview on structure prediction of twilight-zone proteins

Khor BY, Tye GJ, Lim TS, Choong YS

Theor Biol Med Model, 2015;12:15.
PMID: 26338054 DOI: 10.1186/s12976-015-0014-1

Protein structure prediction from amino acid sequence has been one of the most challenging aspects in computational structural biology despite significant progress in recent years showed by critical assessment of protein structure prediction (CASP) experiments. When experimentally determined structures are unavailable, the predictive structures may serve as starting points to study a protein. If the target protein consists of homologous region, high-resolution (typically <1.5 Å) model can be built via comparative modelling. However, when confronted with low sequence similarity of the target protein (also known as twilight-zone protein, sequence identity with available templates is less than 30%), the protein structure prediction has to be initiated from scratch. Traditionally, twilight-zone proteins can be predicted via threading or ab initio method. Based on the current trend, combination of different methods brings an improved success in the prediction of twilight-zone proteins. In this mini review, the methods, progresses and challenges for the prediction of twilight-zone proteins were discussed.

Matched MeSH terms: Amino Acid Sequence

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