Displaying publications 1 - 20 of 39 in total

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  1. Ee SF, Oh JM, Mohd Noor N, Kwon TR, Mohamed-Hussein ZA, Ismail I, et al.
    Mol Biol Rep, 2013 Mar;40(3):2231-41.
    PMID: 23187733 DOI: 10.1007/s11033-012-2286-4
    The importance of plant secondary metabolites for both mankind and the plant itself has long been established. However, despite extensive research on plant secondary metabolites, plant secondary metabolism and its regulation still remained poorly characterized. In this present study, cDNA-amplified fragment length polymorphism (cDNA-AFLP) transcript profiling was applied to generate the expression profiles of Polygonum minus in response to salicylic acid (SA) and methyl jasmonate (MeJA) elicitations. This study reveals two different sets of genes induced by SA and MeJA, respectively where stress-related genes were proved to lead to the expression of genes involved in plant secondary metabolite biosynthetic pathways. A total of 98 transcript-derived fragments (TDFs) were up-regulated, including 46 from SA-treated and 52 from MeJA-treated samples. The cDNA-AFLP transcripts generated using 64 different Mse1/Taq1 primer combinations showed that treatments with SA and MeJA induced genes mostly involved in scavenging reactive oxygen species, including zeaxanthin epoxidase, cytosolic ascorbate peroxidase 1 and peroxidase. Of these stress-related genes, 15 % of other annotated TDFs are involved mainly in secondary metabolic processes where among these, two genes encoding (+)-delta cadinene synthase and cinnamoyl-CoA reductase were highlighted.
  2. Govender N, Senan S, Mohamed-Hussein ZA, Ratnam W
    Genom Data, 2017 Sep;13:11-14.
    PMID: 28626637 DOI: 10.1016/j.gdata.2017.05.008
    Shoot and inflorescence are central physiological and developmental tissues of plants. Flowering is one of the most important agronomic traits for improvement of crop yield. To analyze the vegetative to reproductive tissue transition in Jatropha curcas, gene expression profiles were generated from shoot and inflorescence tissues. RNA isolated from both tissues was sequenced using the Ilumina HiSeq 2500 platform. Differential gene expression analysis identified key biological processes associated with vegetative to reproductive tissue transition. The present data for J. curcas may inform the design of breeding strategies particularly with respect to reproductive tissue transition. The raw data of this study has been deposited in the NCBI's Sequence Read Archive (SRA) database with the accession number SRP090662.
  3. Loke KK, Rahnamaie-Tajadod R, Yeoh CC, Goh HH, Mohamed-Hussein ZA, Zainal Z, et al.
    PeerJ, 2017;5:e2938.
    PMID: 28265493 DOI: 10.7717/peerj.2938
    BACKGROUND: Polygonum minus is an herbal plant in the Polygonaceae family which is rich in ethnomedicinal plants. The chemical composition and characteristic pungent fragrance of Polygonum minus have been extensively studied due to its culinary and medicinal properties. There are only a few transcriptome sequences available for species from this important family of medicinal plants. The limited genetic information from the public expressed sequences tag (EST) library hinders further study on molecular mechanisms underlying secondary metabolite production.

    METHODS: In this study, we performed a hybrid assembly of 454 and Illumina sequencing reads from Polygonum minus root and leaf tissues, respectively, to generate a combined transcriptome library as a reference.

    RESULTS: A total of 34.37 million filtered and normalized reads were assembled into 188,735 transcripts with a total length of 136.67 Mbp. We performed a similarity search against all the publicly available genome sequences and found similarity matches for 163,200 (86.5%) of Polygonum minus transcripts, largely from Arabidopsis thaliana (58.9%). Transcript abundance in the leaf and root tissues were estimated and validated through RT-qPCR of seven selected transcripts involved in the biosynthesis of phenylpropanoids and flavonoids. All the transcripts were annotated against KEGG pathways to profile transcripts related to the biosynthesis of secondary metabolites.

    DISCUSSION: This comprehensive transcriptome profile will serve as a useful sequence resource for molecular genetics and evolutionary research on secondary metabolite biosynthesis in Polygonaceae family. Transcriptome assembly of Polygonum minus can be accessed at http://prims.researchfrontier.org/index.php/dataset/transcriptome.

  4. Harun S, Abdullah-Zawawi MR, A-Rahman MRA, Muhammad NAN, Mohamed-Hussein ZA
    Database (Oxford), 2019 01 01;2019.
    PMID: 30793170 DOI: 10.1093/database/baz021
    Plants produce a wide range of secondary metabolites that play important roles in plant defense and immunity, their interaction with the environment and symbiotic associations. Sulfur-containing compounds (SCCs) are a group of important secondary metabolites produced in members of the Brassicales order. SCCs constitute various groups of phytochemicals, but not much is known about them. Findings from previous studies on SCCs were scattered in published literatures, hence SuCComBase was developed to store all molecular information related to the biosynthesis of SCCs. Information that includes genes, proteins and compounds that are involved in the SCC biosynthetic pathway was manually identified from databases and published scientific literatures. Sets of co-expression data was analyzed to search for other possible (previously unknown) genes that might be involved in the biosynthesis of SCC. These genes were named as potential SCC-related encoding genes. A total of 147 known and 92 putative Arabidopsis thaliana SCC-related genes from literatures were used to identify other potential SCC-related encoding genes. We identified 778 potential SCC-related encoding genes, 4026 homologs to the SCC-related encoding genes and 116 SCCs as shown on SuCComBase homepage. Data entries are searchable from the Main page, Search, Browse and Datasets tabs. Users can easily download all data stored in SuCComBase. All publications related to SCCs are also indexed in SuCComBase, which is currently the first and only database dedicated to plant SCCs. SuCComBase aims to become a manually curated and au fait knowledge-based repository for plant SCCs.
  5. Tan CS, Hassan M, Mohamed Hussein ZA, Ismail I, Ho KL, Ng CL, et al.
    Plant Physiol Biochem, 2018 Feb;123:359-368.
    PMID: 29304481 DOI: 10.1016/j.plaphy.2017.12.033
    Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp280, Leu294 and Ala303). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily.
  6. Hawari AH, Mohamed-Hussein ZA
    BMC Bioinformatics, 2010;11:83.
    PMID: 20144236 DOI: 10.1186/1471-2105-11-83
    The development and simulation of dynamic models of terpenoid biosynthesis has yielded a systems perspective that provides new insights into how the structure of this biochemical pathway affects compound synthesis. These insights may eventually help identify reactions that could be experimentally manipulated to amplify terpenoid production. In this study, a dynamic model of the terpenoid biosynthesis pathway was constructed based on the Hybrid Functional Petri Net (HFPN) technique. This technique is a fusion of three other extended Petri net techniques, namely Hybrid Petri Net (HPN), Dynamic Petri Net (HDN) and Functional Petri Net (FPN).
  7. Govender N, Senan S, Mohamed-Hussein ZA, Isa MNM, Yaakob Z, Ratnam W
    Data Brief, 2018 Dec;21:71-74.
    PMID: 30338276 DOI: 10.1016/j.dib.2018.09.081
    Jatropha curcas L. or the physic nut is a monoecious shrub belonging to the Euphorbiaceae family. The plant is an ideal feedstock for biodiesel production; oil-rich seed (37-42%), has a broad range of growth habitat such as arid, semi-arid and tropical and a relatively feasible process for conversion of crude oil into biodiesel. The major constraint affecting the success of large-scale J. curcas plantation is seed yield inconsistency. Numerous research projects conducted on J. curcas with integrated genetic, genomic and transcriptomic approaches have been applied on the leaf, apical meristem, flower, root and fruit tissues. However, to date, no genomics data of J. curcas shoot system are publicly available, despite its importance in understanding flowering, fruiting and seed set qualities targeted for yield improvement. Here, we present eighteen sets of shoot and inflorescence transcriptomes generated from J. curcas plants with contrasting yields. Raw reads of the RNA-seq data are found in NCBI׳s Sequence Read Archive (SRA) database with the accession number SRP090662 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP090662). This transcriptomic data could be integrated with the present genomic resources for in depth understanding of J. curcas reproductive system.
  8. Zainal-Abidin RA, Zainal Z, Mohamed-Hussein ZA, Abu-Bakar N, Ab Razak MSF, Simoh S, et al.
    Data Brief, 2020 Jun;30:105432.
    PMID: 32280737 DOI: 10.1016/j.dib.2020.105432
    Pigmented rice is enriched with antioxidants, macro- and micronutrients. A comprehensive investigation of the gene expression patterns among the pigmented rice varieties would help to understand the cellular mechanism and biological processes of rice grain pigmentation. Hence, we performed RNA sequencing and analysis on the whole grain of dehusked mature seeds of selected six Malaysian rice varieties with varying grain pigmentations. These varieties were black rice (BALI and Pulut Hitam 9), red rice (MRM16 and MRQ100) and white rice (MR297 and MRQ76). Illumina HiSeq™ 4000 sequencer was used to generate total raw nucleotides of approximately 53 Gb in size. From 353,937,212 total paired-end raw reads, 340,131,496 total clean reads were obtained. The raw reads were deposited into European Nucleotide Archive (ENA) database and can be accessed via accession number PRJEB34340. This dataset allows us to identify and profile all expressed genes with functions related to nutritional traits (i.e. antioxidants, folate and amylose content) and quality trait (i.e. aroma) across both pigmented and non-pigmented rice varieties. In addition, the transcriptome data obtained will be valuable for discovery of potential gene markers and functional SNPs related to functional traits to assist in rice breeding programme.
  9. Loke KK, Rahnamaie-Tajadod R, Yeoh CC, Goh HH, Mohamed-Hussein ZA, Mohd Noor N, et al.
    Genom Data, 2016 Mar;7:12-3.
    PMID: 26981350 DOI: 10.1016/j.gdata.2015.11.003
    Polygonum minus plant is rich in secondary metabolites, especially terpenoids and flavonoids. Present study generates transcriptome resource for P. minus to decipher its secondary metabolite biosynthesis pathways. Raw reads and the transcriptome assembly project have been deposited at GenBank under the accessions SRX313492 (root) and SRX669305 (leaf) respectively.
  10. Ahmad-Sohdi NA, Seman-Kamarulzaman AF, Mohamed-Hussein ZA, Hassan M
    PLoS One, 2015;10(11):e0143310.
    PMID: 26600471 DOI: 10.1371/journal.pone.0143310
    Juvenile hormones have attracted attention as safe and selective targets for the design and development of environmentally friendly and biorational insecticides. In the juvenile hormone III biosynthetic pathway, the enzyme farnesol dehydrogenase catalyzes the oxidation of farnesol to farnesal. In this study, farnesol dehydrogenase was extracted from Polygonum minus leaves and purified 204-fold to apparent homogeneity by ion-exchange chromatography using DEAE-Toyopearl, SP-Toyopearl, and Super-Q Toyopearl, followed by three successive purifications by gel filtration chromatography on a TSK-gel GS3000SW. The enzyme is a heterodimer comprised of subunits with molecular masses of 65 kDa and 70 kDa. The optimum temperature and pH were 35°C and pH 9.5, respectively. Activity was inhibited by sulfhydryl reagents, metal-chelating agents and heavy metal ions. The enzyme utilized both NAD+ and NADP+ as coenzymes with Km values of 0.74 mM and 40 mM, respectively. Trans, trans-farnesol was the preferred substrate for the P. minus farnesol dehydrogenase. Geometrical isomers of trans, trans-farnesol, cis, trans-farnesol and cis, cis-farnesol were also oxidized by the enzyme with lower activity. The Km values for trans, trans-farnesol, cis, trans-farnesol and cis, cis-farnesol appeared to be 0.17 mM, 0.33 mM and 0.42 mM, respectively. The amino acid sequences of 4 tryptic peptides of the enzyme were analyzed by MALDI-TOF/TOF-MS spectrometry, and showed no significant similarity to those of previously reported farnesol dehydrogenases. These results suggest that the purified enzyme is a novel NAD(P)+-dependent farnesol dehydrogenase. The purification and characterization established in the current study will serve as a basis to provide new information for recombinant production of the enzyme. Therefore, recombinant farnesol dehydrogenase may provide a useful molecular tool in manipulating juvenile hormone biosynthesis to generate transgenic plants for pest control.
  11. Ramly B, Afiqah-Aleng N, Mohamed-Hussein ZA
    Int J Mol Sci, 2019 Jun 18;20(12).
    PMID: 31216618 DOI: 10.3390/ijms20122959
    Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein-protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher's exact test and comorbidity data were used to identify PCOS-disease subnetworks. Pathway enrichment analysis was performed on the PCOS-disease subnetworks to identify significant pathways that are highly involved in the PCOS-disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension.
  12. Harun S, Afiqah-Aleng N, Karim MB, Altaf Ul Amin M, Kanaya S, Mohamed-Hussein ZA
    PeerJ, 2021;9:e11876.
    PMID: 34430080 DOI: 10.7717/peerj.11876
    Background: Glucosinolates (GSLs) are plant secondary metabolites that contain nitrogen-containing compounds. They are important in the plant defense system and known to provide protection against cancer in humans. Currently, increasing the amount of data generated from various omics technologies serves as a hotspot for new gene discovery. However, sometimes sequence similarity searching approach is not sufficiently effective to find these genes; hence, we adapted a network clustering approach to search for potential GSLs genes from the Arabidopsis thaliana co-expression dataset.

    Methods: We used known GSL genes to construct a comprehensive GSL co-expression network. This network was analyzed with the DPClusOST algorithm using a density of 0.5. 0.6. 0.7, 0.8, and 0.9. Generating clusters were evaluated using Fisher's exact test to identify GSL gene co-expression clusters. A significance score (SScore) was calculated for each gene based on the generated p-value of Fisher's exact test. SScore was used to perform a receiver operating characteristic (ROC) study to classify possible GSL genes using the ROCR package. ROCR was used in determining the AUC that measured the suitable density value of the cluster for further analysis. Finally, pathway enrichment analysis was conducted using ClueGO to identify significant pathways associated with the GSL clusters.

    Results: The density value of 0.8 showed the highest area under the curve (AUC) leading to the selection of thirteen potential GSL genes from the top six significant clusters that include IMDH3, MVP1, T19K24.17, MRSA2, SIR, ASP4, MTO1, At1g21440, HMT3, At3g47420, PS1, SAL1, and At3g14220. A total of Four potential genes (MTO1, SIR, SAL1, and IMDH3) were identified from the pathway enrichment analysis on the significant clusters. These genes are directly related to GSL-associated pathways such as sulfur metabolism and valine, leucine, and isoleucine biosynthesis. This approach demonstrates the ability of the network clustering approach in identifying potential GSL genes which cannot be found from the standard similarity search.

  13. Govender N, Zulkifli NS, Badrul Hisham NF, Ab Ghani NS, Mohamed-Hussein ZA
    PeerJ, 2022;10:e14168.
    PMID: 36518265 DOI: 10.7717/peerj.14168
    BACKGROUND: Pea eggplant (Solanum torvum Swartz) commonly known as turkey berry or 'terung pipit' in Malay is a vegetable plant widely consumed by the local community in Malaysia. The shrub bears pea-like turkey berry fruits (TBFs), rich in phytochemicals of medicinal interest. The TBF phytochemicals hold a wide spectrum of pharmacological properties. In this study, the TBF phytochemicals' potential inhibitory properties were evaluated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the Coronavirus disease 2019 (COVID-19). The TBF polyphenols were screened against SARS-CoV receptors via molecular docking and the best receptor-ligand complex was validated further by molecular dynamics (MD) simulation.

    METHOD: The SARS-CoV receptor structure files (viral structural components) were retrieved from the Protein Data Bank (PDB) database: membrane protein (PDB ID: 3I6G), main protease (PDB ID: 5RE4), and spike glycoproteins (PDB ID: 6VXX and 6VYB). The receptor binding pocket regions were identified by Discovery Studio (BIOVIA) for targeted docking with TBF polyphenols (genistin, kaempferol, mellein, rhoifolin and scutellarein). The ligand and SARS-CoV family receptor structure files were pre-processed using the AutoDock tools. Molecular docking was performed with the Lamarckian genetic algorithm using AutoDock Vina 4.2 software. The best pose (ligand-receptor complex) from the molecular docking analysis was selected based on the minimum binding energy (MBE) and extent of structural interactions, as indicated by BIOVIA visualization tool. The selected complex was validated by a 100 ns MD simulation run using the GROMACS software. The dynamic behaviour and stability of the receptor-ligand complex were evaluated by the root mean square displacement (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), solvent accessible surface volume (SASV) and number of hydrogen bonds.

    RESULTS: At RMSD = 0, the TBF polyphenols showed fairly strong physical interactions with SARS-CoV receptors under all possible combinations. The MBE of TBF polyphenol-bound SARS CoV complexes ranged from -4.6 to -8.3 kcal/mol. Analysis of the structural interactions showed the presence of hydrogen bonds, electrostatic and hydrophobic interactions between the receptor residues (RR) and ligands atoms. Based on the MBE values, the 3I6G-rhoifolin (MBE = -8.3 kcal/mol) and 5RE4-genistin (MBE = -7.6 kcal/mol) complexes were ranked with the least value. However, the latter showed a greater extent of interactions between the RRs and the ligand atoms and thus was further validated by MD simulation. The MD simulation parameters of the 5RE4-genistin complex over a 100 ns run indicated good structural stability with minimal flexibility within genistin binding pocket region. The findings suggest that S. torvum polyphenols hold good therapeutics potential in COVID-19 management.

  14. Afiqah-Aleng N, Harun S, A-Rahman MRA, Nor Muhammad NA, Mohamed-Hussein ZA
    Database (Oxford), 2017 Jan 01;2017.
    PMID: 31725861 DOI: 10.1093/database/bax098
    Polycystic ovarian syndrome (PCOS) is one of the main causes of infertility and affects 5-20% women of reproductive age. Despite the increased prevalence of PCOS, the mechanisms involved in its pathogenesis and pathophysiology remains unclear. The expansion of omics on studying the mechanisms of PCOS has lead into vast amounts of proteins related to PCOS resulting to a challenge in collating and depositing this deluge of data into one place. A knowledge-based repository named as PCOSBase was developed to systematically store all proteins related to PCOS. These proteins were compiled from various online databases and published expression studies. Rigorous criteria were developed to identify those that were highly related to PCOS. They were manually curated and analysed to provide additional information on gene ontologies, pathways, domains, tissue localizations and diseases that associate with PCOS. Other proteins that might interact with PCOS-related proteins identified from this study were also included. Currently, 8185 PCOS-related proteins were identified and assigned to 13 237 gene ontology vocabulary, 1004 pathways, 7936 domains, 29 disease classes, 1928 diseases, 91 tissues and 320 472 interactions. All publications related to PCOS are also indexed in PCOSBase. Data entries are searchable in the main page, search, browse and datasets tabs. Protein advanced search is provided to search for specific proteins. To date, PCOSBase has the largest collection of PCOS-related proteins. PCOSBase aims to become a self-contained database that can be used to further understand the PCOS pathogenesis and towards the identification of potential PCOS biomarkers. Database URL: http://pcosbase.org.
  15. Seman-Kamarulzaman AF, Mohamed-Hussein ZA, Ng CL, Hassan M
    PLoS One, 2016;11(8):e0161707.
    PMID: 27560927 DOI: 10.1371/journal.pone.0161707
    Juvenile Hormone III is of great concern due to negative effects on major developmental and reproductive maturation in insect pests. Thus, the elucidation of enzymes involved JH III biosynthetic pathway has become increasing important in recent years. One of the enzymes in the JH III biosynthetic pathway that remains to be isolated and characterized is farnesal dehydrogenase, an enzyme responsible to catalyze the oxidation of farnesal into farnesoic acid. A novel NAD+-farnesal dehydrogenase of Polygonum minus was purified (315-fold) to apparent homogeneity in five chromatographic steps. The purification procedures included Gigacap S-Toyopearl 650M, Gigacap Q-Toyopearl 650M, and AF-Blue Toyopearl 650ML, followed by TSK Gel G3000SW chromatographies. The enzyme, with isoelectric point of 6.6 is a monomeric enzyme with a molecular mass of 70 kDa. The enzyme was relatively active at 40°C, but was rapidly inactivated above 45°C. The optimal temperature and pH of the enzyme were found to be 35°C and 9.5, respectively. The enzyme activity was inhibited by sulfhydryl agent, chelating agent, and metal ion. The enzyme was highly specific for farnesal and NAD+. Other terpene aldehydes such as trans- cinnamaldehyde, citral and α- methyl cinnamaldehyde were also oxidized but in lower activity. The Km values for farnesal, citral, trans- cinnamaldehyde, α- methyl cinnamaldehyde and NAD+ were 0.13, 0.69, 0.86, 1.28 and 0.31 mM, respectively. The putative P. minus farnesal dehydrogenase that's highly specific towards farnesal but not to aliphatic aldehydes substrates suggested that the enzyme is significantly different from other aldehyde dehydrogenases that have been reported. The MALDI-TOF/TOF-MS/MS spectrometry further identified two peptides that share similarity to those of previously reported aldehyde dehydrogenases. In conclusion, the P. minus farnesal dehydrogenase may represent a novel plant farnesal dehydrogenase that exhibits distinctive substrate specificity towards farnesal. Thus, it was suggested that this novel enzyme may be functioning specifically to oxidize farnesal in the later steps of JH III pathway. This report provides a basic understanding for recombinant production of this particular enzyme. Other strategies such as adding His-tag to the protein makes easy the purification of the protein which is completely different to the native protein. Complete sequence, structure and functional analysis of the enzyme will be important for developing insect-resistant crop plants by deployment of transgenic plant.
  16. Rosilan NF, Jamali MAM, Sufira SA, Waiho K, Fazhan H, Ismail N, et al.
    PLoS One, 2024;19(1):e0297759.
    PMID: 38266027 DOI: 10.1371/journal.pone.0297759
    Shrimp aquaculture contributes significantly to global economic growth, and the whiteleg shrimp, Penaeus vannamei, is a leading species in this industry. However, Vibrio parahaemolyticus infection poses a major challenge in ensuring the success of P. vannamei aquaculture. Despite its significance in this industry, the biological knowledge of its pathogenesis remains unclear. Hence, this study was conducted to identify the interaction sites and binding affinity between several immune-related proteins of P. vannamei with V. parahaemolyticus proteins associated with virulence factors. Potential interaction sites and the binding affinity between host and pathogen proteins were identified using molecular docking and dynamics (MD) simulation. The P. vannamei-V. parahaemolyticus protein-protein interaction of Complex 1 (Ferritin-HrpE/YscL family type III secretion apparatus protein), Complex 2 (Protein kinase domain-containing protein-Chemotaxis CheY protein), and Complex 3 (GPCR-Chemotaxis CheY protein) was found to interact with -4319.76, -5271.39, and -4725.57 of the docked score and the formation of intermolecular bonds at several interacting residues. The docked scores of Complex 1, Complex 2, and Complex 3 were validated using MD simulation analysis, which revealed these complexes greatly contribute to the interactions between P. vannamei and V. parahaemolyticus proteins, with binding free energies of -22.50 kJ/mol, -30.20 kJ/mol, and -26.27 kJ/mol, respectively. This finding illustrates the capability of computational approaches to search for molecular binding sites between host and pathogen, which could increase the knowledge of Vibrio spp. infection on shrimps, which then can be used to assist in the development of effective treatment.
  17. Zifruddin AN, Mohamad-Khalid KA, Suhaimi SA, Mohamed-Hussein ZA, Hassan M
    Biosci Biotechnol Biochem, 2021 Jun 24;85(7):1628-1638.
    PMID: 33890631 DOI: 10.1093/bbb/zbab072
    Juvenile hormone III (JH III) plays an important role in insect reproduction, development, and behavior. The second branch of JH III production includes oxidation of farnesol to farnesal by farnesol dehydrogenase. This study reported the identification and characterization of Plutella xylostella farnesol dehydrogenase (PxFoLDH). Our results showed that PxFoLDH belongs to the short-chain dehydrogenase/reductase superfamily, consisting of a single domain with a structurally conserved Rossman fold, an NAD(P) (H)-binding region and a structurally diverse C-terminal region. The purified enzyme displayed maximum activity at 55$\ $°C with pH 9.5 and was stable in the temperature below 70$\ ^\circ $C. PxFoLDH was determined to be a monomer with a relative molecular weight of 27 kDa and highly specific for trans, trans-farnesol, and NADP+. Among analog inhibitors tested, farnesyl acetate was the most effective inhibitor with the lowest Ki value of 0.02 µm. Our findings showed this purified enzyme may represent as NADP+-farnesol dehydrogenase.
  18. Remali J, Aizat WM, Ng CL, Lim YC, Mohamed-Hussein ZA, Fazry S
    PeerJ, 2020;8:e9197.
    PMID: 32509463 DOI: 10.7717/peerj.9197
    Background: DNA double strand break repair is important to preserve the fidelity of our genetic makeup after DNA damage. Rad50 is one of the components in MRN complex important for DNA repair mechanism. Rad50 mutations can lead to microcephaly, mental retardation and growth retardation in human. However, Rad50 mutations in human and other organisms have never been gathered and heuristically compared for their deleterious effects. It is important to assess the conserved region in Rad50 and its homolog to identify vital mutations that can affect functions of the protein.

    Method: In this study, Rad50 mutations were retrieved from SNPeffect 4.0 database and literature. Each of the mutations was analyzed using various bioinformatic analyses such as PredictSNP, MutPred, SNPeffect 4.0, I-Mutant and MuPro to identify its impact on molecular mechanism, biological function and protein stability, respectively.

    Results: We identified 103 mostly occurred mutations in the Rad50 protein domains and motifs, which only 42 mutations were classified as most deleterious. These mutations are mainly situated at the specific motifs such as Walker A, Q-loop, Walker B, D-loop and signature motif of the Rad50 protein. Some of these mutations were predicted to negatively affect several important functional sites that play important roles in DNA repair mechanism and cell cycle signaling pathway, highlighting Rad50 crucial role in this process. Interestingly, mutations located at non-conserved regions were predicted to have neutral/non-damaging effects, in contrast with previous experimental studies that showed deleterious effects. This suggests that software used in this study may have limitations in predicting mutations in non-conserved regions, implying further improvement in their algorithm is needed. In conclusion, this study reveals the priority of acid substitution associated with the genetic disorders. This finding highlights the vital roles of certain residues such as K42E, C681A/S, CC684R/S, S1202R, E1232Q and D1238N/A located in Rad50 conserved regions, which can be considered for a more targeted future studies.

  19. Afiqah-Aleng N, Altaf-Ul-Amin M, Kanaya S, Mohamed-Hussein ZA
    Reprod Biomed Online, 2020 Feb;40(2):319-330.
    PMID: 32001161 DOI: 10.1016/j.rbmo.2019.11.012
    RESEARCH QUESTION: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with diverse clinical implications, such as infertility, metabolic disorders, cardiovascular diseases and psychological problems among others. The heterogeneity of conditions found in PCOS contribute to its various phenotypes, leading to difficulties in identifying proteins involved in this abnormality. Several studies, however, have shown the feasibility in identifying molecular evidence underlying other diseases using graph cluster analysis. Therefore, is it possible to identify proteins and pathways related to PCOS using the same approach?

    METHODS: Known PCOS-related proteins (PCOSrp) from PCOSBase and DisGeNET were integrated with protein-protein interactions (PPI) information from Human Integrated Protein-Protein Interaction reference to construct a PCOS PPI network. The network was clustered with DPClusO algorithm to generate clusters, which were evaluated using Fisher's exact test. Pathway enrichment analysis using gProfileR was conducted to identify significant pathways.

    RESULTS: The statistical significance of the identified clusters has successfully predicted 138 novel PCOSrp with 61.5% reliability and, based on Cronbach's alpha, this prediction is acceptable. Androgen signalling pathway and leptin signalling pathway were among the significant PCOS-related pathways corroborating the information obtained from the clinical observation, where androgen signalling pathway is responsible in producing male hormones in women with PCOS, whereas leptin signalling pathway is involved in insulin sensitivity.

    CONCLUSIONS: These results show that graph cluster analysis can provide additional insight into the pathobiology of PCOS, as the pathways identified as statistically significant correspond to earlier biological studies. Therefore, integrative analysis can reveal unknown mechanisms, which may enable the development of accurate diagnosis and effective treatment in PCOS.

  20. Ee SF, Mohamed-Hussein ZA, Othman R, Shaharuddin NA, Ismail I, Zainal Z
    ScientificWorldJournal, 2014;2014:840592.
    PMID: 24678279 DOI: 10.1155/2014/840592
    Polygonum minus is an aromatic plant, which contains high abundance of terpenoids, especially the sesquiterpenes C15H24. Sesquiterpenes were believed to contribute to the many useful biological properties in plants. This study aimed to functionally characterize a full length sesquiterpene synthase gene from P. minus. P. minus sesquiterpene synthase (PmSTS) has a complete open reading frame (ORF) of 1689 base pairs encoding a 562 amino acid protein. Similar to other sesquiterpene synthases, PmSTS has two large domains: the N-terminal domain and the C-terminal metal-binding domain. It also consists of three conserved motifs: the DDXXD, NSE/DTE, and RXR. A three-dimensional protein model for PmSTS built clearly distinguished the two main domains, where conserved motifs were highlighted. We also constructed a phylogenetic tree, which showed that PmSTS belongs to the angiosperm sesquiterpene synthase subfamily Tps-a. To examine the function of PmSTS, we expressed this gene in Arabidopsis thaliana. Two transgenic lines, designated as OE3 and OE7, were further characterized, both molecularly and functionally. The transgenic plants demonstrated smaller basal rosette leaves, shorter and fewer flowering stems, and fewer seeds compared to wild type plants. Gas chromatography-mass spectrometry analysis of the transgenic plants showed that PmSTS was responsible for the production of β -sesquiphellandrene.
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