Displaying publications 1 - 20 of 38 in total

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  1. Fulltext The Glaciozyma antarctica genome reveals an array of systems that provide sustained responses towards temperature variations in a persistently cold habitat
    Firdaus-Raih M, Hashim NHF, Bharudin I, Abu Bakar MF, Huang KK, Alias H, et al.
    PLoS One, 2018;13(1):e0189947.
    PMID: 29385175 DOI: 10.1371/journal.pone.0189947
    Extremely low temperatures present various challenges to life that include ice formation and effects on metabolic capacity. Psyhcrophilic microorganisms typically have an array of mechanisms to enable survival in cold temperatures. In this study, we sequenced and analysed the genome of a psychrophilic yeast isolated in the Antarctic region, Glaciozyma antarctica. The genome annotation identified 7857 protein coding sequences. From the genome sequence analysis we were able to identify genes that encoded for proteins known to be associated with cold survival, in addition to annotating genes that are unique to G. antarctica. For genes that are known to be involved in cold adaptation such as anti-freeze proteins (AFPs), our gene expression analysis revealed that they were differentially transcribed over time and in response to different temperatures. This indicated the presence of an array of adaptation systems that can respond to a changing but persistent cold environment. We were also able to validate the activity of all the AFPs annotated where the recombinant AFPs demonstrated anti-freeze capacity. This work is an important foundation for further collective exploration into psychrophilic microbiology where among other potential, the genes unique to this species may represent a pool of novel mechanisms for cold survival.
  2. Fulltext Evidence-based gene models for structural and functional annotations of the oil palm genome
    Chan KL, Tatarinova TV, Rosli R, Amiruddin N, Azizi N, Halim MAA, et al.
    Biol. Direct, 2017 Sep 08;12(1):21.
    PMID: 28886750 DOI: 10.1186/s13062-017-0191-4
    BACKGROUND: Oil palm is an important source of edible oil. The importance of the crop, as well as its long breeding cycle (10-12 years) has led to the sequencing of its genome in 2013 to pave the way for genomics-guided breeding. Nevertheless, the first set of gene predictions, although useful, had many fragmented genes. Classification and characterization of genes associated with traits of interest, such as those for fatty acid biosynthesis and disease resistance, were also limited. Lipid-, especially fatty acid (FA)-related genes are of particular interest for the oil palm as they specify oil yields and quality. This paper presents the characterization of the oil palm genome using different gene prediction methods and comparative genomics analysis, identification of FA biosynthesis and disease resistance genes, and the development of an annotation database and bioinformatics tools.

    RESULTS: Using two independent gene-prediction pipelines, Fgenesh++ and Seqping, 26,059 oil palm genes with transcriptome and RefSeq support were identified from the oil palm genome. These coding regions of the genome have a characteristic broad distribution of GC3 (fraction of cytosine and guanine in the third position of a codon) with over half the GC3-rich genes (GC3 ≥ 0.75286) being intronless. In comparison, only one-seventh of the oil palm genes identified are intronless. Using comparative genomics analysis, characterization of conserved domains and active sites, and expression analysis, 42 key genes involved in FA biosynthesis in oil palm were identified. For three of them, namely EgFABF, EgFABH and EgFAD3, segmental duplication events were detected. Our analysis also identified 210 candidate resistance genes in six classes, grouped by their protein domain structures.

    CONCLUSIONS: We present an accurate and comprehensive annotation of the oil palm genome, focusing on analysis of important categories of genes (GC3-rich and intronless), as well as those associated with important functions, such as FA biosynthesis and disease resistance. The study demonstrated the advantages of having an integrated approach to gene prediction and developed a computational framework for combining multiple genome annotations. These results, available in the oil palm annotation database ( http://palmxplore.mpob.gov.my ), will provide important resources for studies on the genomes of oil palm and related crops.

    REVIEWERS: This article was reviewed by Alexander Kel, Igor Rogozin, and Vladimir A. Kuznetsov.

  3. Fulltext Structural and functional analyses of Burkholderia pseudomallei BPSL1038 reveal a Cas-2/VapD nuclease sub-family
    Shaibullah S, Shuhaimi N, Ker DS, Mohd-Sharif N, Ho KL, Teh AH, et al.
    Commun Biol, 2023 Sep 08;6(1):920.
    PMID: 37684342 DOI: 10.1038/s42003-023-05265-4
    Burkholderia pseudomallei is a highly versatile pathogen with ~25% of its genome annotated to encode hypothetical proteins. One such hypothetical protein, BPSL1038, is conserved across seven bacterial genera and 654 Burkholderia spp. Here, we present a 1.55 Å resolution crystal structure of BPSL1038. The overall structure folded into a modified βαββαβα ferredoxin fold similar to known Cas2 nucleases. The Cas2 equivalent catalytic aspartate (D11) pairs are conserved in BPSL1038 although B. pseudomallei has no known CRISPR associated system. Functional analysis revealed that BPSL1038 is a nuclease with endonuclease activity towards double-stranded DNA. The DNase activity is divalent ion independent and optimum at pH 6. The concentration of monovalent ions (Na+ and K+) is crucial for nuclease activity. An active site with a unique D11(X20)SST motif was identified and proposed for BPSL1038 and its orthologs. Structure modelling indicates the catalytic role of the D11(X20)SST motif and that the arginine residues R10 and R30 may interact with the nucleic acid backbone. The structural similarity of BPSL1038 to Cas2 proteins suggests that BPSL1038 may represent a sub-family of nucleases that share a common ancestor with Cas2.
  4. Structural dissection of two redox proteins from the shipworm symbiont Teredinibacter turnerae
    Rajagopal BS, Yates N, Smith J, Paradisi A, Tétard-Jones C, Willats WGT, et al.
    IUCrJ, 2024 Mar 01;11(Pt 2):260-274.
    PMID: 38446458 DOI: 10.1107/S2052252524001386
    The discovery of lytic polysaccharide monooxygenases (LPMOs), a family of copper-dependent enzymes that play a major role in polysaccharide degradation, has revealed the importance of oxidoreductases in the biological utilization of biomass. In fungi, a range of redox proteins have been implicated as working in harness with LPMOs to bring about polysaccharide oxidation. In bacteria, less is known about the interplay between redox proteins and LPMOs, or how the interaction between the two contributes to polysaccharide degradation. We therefore set out to characterize two previously unstudied proteins from the shipworm symbiont Teredinibacter turnerae that were initially identified by the presence of carbohydrate binding domains appended to uncharacterized domains with probable redox functions. Here, X-ray crystal structures of several domains from these proteins are presented together with initial efforts to characterize their functions. The analysis suggests that the target proteins are unlikely to function as LPMO electron donors, raising new questions as to the potential redox functions that these large extracellular multi-haem-containing c-type cytochromes may perform in these bacteria.
  5. Unravelling the adaptation strategies employed by Glaciozyma antarctica PI12 on Antarctic sea ice
    Bharudin I, Abu Bakar MF, Hashim NHF, Mat Isa MN, Alias H, Firdaus-Raih M, et al.
    Mar Environ Res, 2018 Jun;137:169-176.
    PMID: 29598997 DOI: 10.1016/j.marenvres.2018.03.007
    Glaciozyma antarctica PI12, is a psychrophilic yeast isolated from Antarctic sea. In this work, Expressed Sequence Tags (EST) from cells exposed to three different temperatures; 15 °C, 0 °C and -12 °C were generated to identify genes associated with cold adaptation. A total of 5376 clones from each library were randomly picked and sequenced. Comparative analyses from the resulting ESTs in each condition identified several groups of genes required for cold adaptation. Additionally, 319 unique transcripts that encoded uncharacterised functions were identified in the -12 °C library and are currently unique to G. antarctica. Gene expression analysis using RT-qPCR revealed two of the unknown genes to be up-regulated at -12 °C compared to 0 °C and 15 °C. These findings further contribute to the collective knowledge into G. antarctica cold adaptation and as a resource for understanding the ecological and physiological tolerance of psychrophilic microbes in general.
  6. Fulltext Perigone Lobe Transcriptome Analysis Provides Insights into Rafflesia cantleyi Flower Development
    Lee XW, Mat-Isa MN, Mohd-Elias NA, Aizat-Juhari MA, Goh HH, Dear PH, et al.
    PLoS One, 2016;11(12):e0167958.
    PMID: 27977777 DOI: 10.1371/journal.pone.0167958
    Rafflesia is a biologically enigmatic species that is very rare in occurrence and possesses an extraordinary morphology. This parasitic plant produces a gigantic flower up to one metre in diameter with no leaves, stem or roots. However, little is known about the floral biology of this species especially at the molecular level. In an effort to address this issue, we have generated and characterised the transcriptome of the Rafflesia cantleyi flower, and performed a comparison with the transcriptome of its floral bud to predict genes that are expressed and regulated during flower development. Approximately 40 million sequencing reads were generated and assembled de novo into 18,053 transcripts with an average length of 641 bp. Of these, more than 79% of the transcripts had significant matches to annotated sequences in the public protein database. A total of 11,756 and 7,891 transcripts were assigned to Gene Ontology categories and clusters of orthologous groups respectively. In addition, 6,019 transcripts could be mapped to 129 pathways in Kyoto Encyclopaedia of Genes and Genomes Pathway database. Digital abundance analysis identified 52 transcripts with very high expression in the flower transcriptome of R. cantleyi. Subsequently, analysis of differential expression between developing flower and the floral bud revealed a set of 105 transcripts with potential role in flower development. Our work presents a deep transcriptome resource analysis for the developing flower of R. cantleyi. Genes potentially involved in the growth and development of the R. cantleyi flower were identified and provide insights into biological processes that occur during flower development.
  7. Biochemical and in silico structural characterization of a cold-active arginase from the psychrophilic yeast, Glaciozyma antarctica PI12
    Yusof NY, Quay DHX, Kamaruddin S, Jonet MA, Md Illias R, Mahadi NM, et al.
    Extremophiles, 2024 Feb 01;28(1):15.
    PMID: 38300354 DOI: 10.1007/s00792-024-01333-7
    Glaciozyma antarctica PI12 is a psychrophilic yeast isolated from Antarctica. In this work, we describe the heterologous production, biochemical properties and in silico structure analysis of an arginase from this yeast (GaArg). GaArg is a metalloenzyme that catalyses the hydrolysis of L-arginine to L-ornithine and urea. The cDNA of GaArg was reversed transcribed, cloned, expressed and purified as a recombinant protein in Escherichia coli. The purified protein was active against L-arginine as its substrate in a reaction at 20 °C, pH 9. At 10-35 °C and pH 7-9, the catalytic activity of the protein was still present around 50%. Mn2+, Ni2+, Co2+ and K+ were able to enhance the enzyme activity more than two-fold, while GaArg is most sensitive to SDS, EDTA and DTT. The predicted structure model of GaArg showed a very similar overall fold with other known arginases. GaArg possesses predominantly smaller and uncharged amino acids, fewer salt bridges, hydrogen bonds and hydrophobic interactions compared to the other counterparts. GaArg is the first reported arginase that is cold-active, facilitated by unique structural characteristics for its adaptation of catalytic functions at low-temperature environments. The structure and function of cold-active GaArg provide insights into the potentiality of new applications in various biotechnology and pharmaceutical industries.
  8. Fulltext The genome of the Tiger Milk mushroom, Lignosus rhinocerotis, provides insights into the genetic basis of its medicinal properties
    Yap HY, Chooi YH, Firdaus-Raih M, Fung SY, Ng ST, Tan CS, et al.
    BMC Genomics, 2014;15:635.
    PMID: 25073817 DOI: 10.1186/1471-2164-15-635
    The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden or Tiger milk mushroom (Polyporales, Basidiomycota) is a valuable folk medicine for indigenous peoples in Southeast Asia. Despite the increasing interest in this ethnobotanical mushroom, very little is known about the molecular and genetic basis of its medicinal and nutraceutical properties.
  9. Modeling and computational characterization of a Xanthomonas sp. Hypothetical protein identifies a remote ortholog of Burkholderia lethal factor 1
    Muhamad Ismail NAS, Yap SH, Mohamad Yussoff MA, Nor Muhammad NA, Firdaus-Raih M, Quay DHX
    J Biomol Struct Dyn, 2023;41(13):6027-6039.
    PMID: 35862639 DOI: 10.1080/07391102.2022.2100827
    Burkholderia Lethal Factor 1 (BLF1) is a deamidase first characterized in Burkholderia pseudomallei. This enzyme inhibits cellular protein synthesis by deamidating a glutamine residue to a glutamic acid in its target protein, the eukaryotic translation initiation factor 4 A (eIF4A). In this work, we present the characterization of a hypothetical protein from Xanthomonas sp. Leaf131 as the first report of a BLF1 family ortholog outside of the Burkholderia genus. Although standard sequence similarity searches such as BLAST were not able to detect the homology between the Xanthomonas sp. Leaf131 hypothetical protein sequence and BLF1, our computed structure model for the Xanthomonas sp. hypothetical protein revealed structural similarities with an RMSD of 2.7 Å/164 Cα atoms and a TM-score of 0.72 when superposed. Structural comparisons of the Xanthomonas model structure against BLF1 and Escherichia coli cytotoxic necrotizing factor 1 (CNF1) revealed that the conserved signature LXGC motif and putative catalytic residues are structurally aligned thus signifying a level of functional or mechanistic similarity. Protein-protein docking analysis and molecular dynamics simulations also demonstrated that eIF4A could still be a possible target substrate for deamidation by XLF1 as it is for BLF1. We therefore propose that this Xanthomonas hypothetical protein be renamed as Xanthomonas Lethal Factor 1 (XLF1). Our work also provides further evidence of the utility of programs such as AlphaFold in bridging the computational function annotation transfer gap despite very low sequence identities of under 20%.Communicated by Ramaswamy H. Sarma.
  10. Fulltext Comparative analysis of nucleus-encoded plastid-targeting proteins in Rafflesia cantleyi against photosynthetic and non-photosynthetic representatives reveals orthologous systems with potentially divergent functions
    Ng SM, Lee XW, Mat-Isa MN, Aizat-Juhari MA, Adam JH, Mohamed R, et al.
    Sci Rep, 2018 Nov 22;8(1):17258.
    PMID: 30467394 DOI: 10.1038/s41598-018-35173-1
    Parasitic plants are known to discard photosynthesis thus leading to the deletion or loss of the plastid genes. Despite plastid genome reduction in non-photosynthetic plants, some nucleus-encoded proteins are transported back to the plastid to carry out specific functions. In this work, we study such proteins in Rafflesia cantleyi, a member of the holoparasitic genus well-known for producing the largest single flower in the world. Our analyses of three transcriptome datasets, two holoparasites (R. cantleyi and Phelipanche aegyptiaca) and one photosynthetic plant (Arabidopsis thaliana), suggest that holoparasites, such as R. cantleyi, retain some common plastid associated processes such as biosynthesis of amino acids and lipids, but are missing photosynthesis components that can be extensions of these pathways. The reconstruction of two selected biosynthetic pathways involving plastids correlates the trend of plastid retention to pathway complexity - transcriptome evidence for R. cantleyi suggests alternate mechanisms in regulating the plastidial heme and terpenoid backbone biosynthesis pathways. The evolution to holoparasitism from autotrophy trends towards devolving the plastid genes to the nuclear genome despite the functional sites remaining in the plastid, or maintaining non-photosynthetic processes in the plastid, before the eventual loss of the plastid and any site dependent functions.
  11. Fulltext COGNAC: a web server for searching and annotating hydrogen-bonded base interactions in RNA three-dimensional structures
    Firdaus-Raih M, Hamdani HY, Nadzirin N, Ramlan EI, Willett P, Artymiuk PJ
    Nucleic Acids Res, 2014 Jul;42(Web Server issue):W382-8.
    PMID: 24831543 DOI: 10.1093/nar/gku438
    Hydrogen bonds are crucial factors that stabilize a complex ribonucleic acid (RNA) molecule's three-dimensional (3D) structure. Minute conformational changes can result in variations in the hydrogen bond interactions in a particular structure. Furthermore, networks of hydrogen bonds, especially those found in tight clusters, may be important elements in structure stabilization or function and can therefore be regarded as potential tertiary motifs. In this paper, we describe a graph theoretical algorithm implemented as a web server that is able to search for unbroken networks of hydrogen-bonded base interactions and thus provide an accounting of such interactions in RNA 3D structures. This server, COGNAC (COnnection tables Graphs for Nucleic ACids), is also able to compare the hydrogen bond networks between two structures and from such annotations enable the mapping of atomic level differences that may have resulted from conformational changes due to mutations or binding events. The COGNAC server can be accessed at http://mfrlab.org/grafss/cognac.
  12. Fulltext NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules
    Hamdani HY, Appasamy SD, Willett P, Artymiuk PJ, Firdaus-Raih M
    Nucleic Acids Res, 2012 Jul;40(Web Server issue):W35-41.
    PMID: 22661578 DOI: 10.1093/nar/gks513
    Similarities in the 3D patterns of RNA base interactions or arrangements can provide insights into their functions and roles in stabilization of the RNA 3D structure. Nucleic Acids Search for Substructures and Motifs (NASSAM) is a graph theoretical program that can search for 3D patterns of base arrangements by representing the bases as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. The input files for NASSAM are PDB formatted 3D coordinates. This web server can be used to identify matches of base arrangement patterns in a query structure to annotated patterns that have been reported in the literature or that have possible functional and structural stabilization implications. The NASSAM program is freely accessible without any login requirement at http://mfrlab.org/grafss/nassam/.
  13. Fulltext SPRITE and ASSAM: web servers for side chain 3D-motif searching in protein structures
    Nadzirin N, Gardiner EJ, Willett P, Artymiuk PJ, Firdaus-Raih M
    Nucleic Acids Res, 2012 Jul;40(Web Server issue):W380-6.
    PMID: 22573174 DOI: 10.1093/nar/gks401
    Similarities in the 3D patterns of amino acid side chains can provide insights into their function despite the absence of any detectable sequence or fold similarities. Search for protein sites (SPRITE) and amino acid pattern search for substructures and motifs (ASSAM) are graph theoretical programs that can search for 3D amino side chain matches in protein structures, by representing the amino acid side chains as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. Both programs require the input file to be in the PDB format. The objective of using SPRITE is to identify matches of side chains in a query structure to patterns with characterized function. In contrast, a 3D pattern of interest can be searched for existing occurrences in available PDB structures using ASSAM. Both programs are freely accessible without any login requirement. SPRITE is available at http://mfrlab.org/grafss/sprite/ while ASSAM can be accessed at http://mfrlab.org/grafss/assam/.
  14. Fulltext Computational discovery and RT-PCR validation of novel Burkholderia conserved and Burkholderia pseudomallei unique sRNAs
    Khoo JS, Chai SF, Mohamed R, Nathan S, Firdaus-Raih M
    BMC Genomics, 2012;13 Suppl 7:S13.
    PMID: 23282220 DOI: 10.1186/1471-2164-13-S7-S13
    The sRNAs of bacterial pathogens are known to be involved in various cellular roles including environmental adaptation as well as regulation of virulence and pathogenicity. It is expected that sRNAs may also have similar functions for Burkholderia pseudomallei, a soil bacterium that can adapt to diverse environmental conditions, which causes the disease melioidosis and is also able to infect a wide variety of hosts.
  15. ProLysED: an integrated database and meta-server of bacterial protease systems
    Firdaus Raih M, Ahmad HA, Sharum MY, Azizi N, Mohamed R
    Appl. Bioinformatics, 2005;4(2):147-50.
    PMID: 16128617
    Bacterial proteases are an important group of enzymes that have very diverse biochemical and cellular functions. Proteases from prokaryotic sources also have a wide range of uses, either in medicine as pathogenic factors or in industry and therapeutics. ProLysED (Prokaryotic Lysis Enzymes Database), our meta-server integrated database of bacterial proteases, is a useful, albeit very niche, resource. The features include protease classification browsing and searching, organism-specific protease browsing, molecular information and visualisation of protease structures from the Protein Data Bank (PDB) as well as predicted protease structures.
  16. Self-assembly programming of DNA polyominoes
    Ong HS, Syafiq-Rahim M, Kasim NH, Firdaus-Raih M, Ramlan EI
    J Biotechnol, 2016 Oct 20;236:141-51.
    PMID: 27569553 DOI: 10.1016/j.jbiotec.2016.08.017
    Fabrication of functional DNA nanostructures operating at a cellular level has been accomplished through molecular programming techniques such as DNA origami and single-stranded tiles (SST). During implementation, restrictive and constraint dependent designs are enforced to ensure conformity is attainable. We propose a concept of DNA polyominoes that promotes flexibility in molecular programming. The fabrication of complex structures is achieved through self-assembly of distinct heterogeneous shapes (i.e., self-organised optimisation among competing DNA basic shapes) with total flexibility during the design and assembly phases. In this study, the plausibility of the approach is validated using the formation of multiple 3×4 DNA network fabricated from five basic DNA shapes with distinct configurations (monomino, tromino and tetrominoes). Computational tools to aid the design of compatible DNA shapes and the structure assembly assessment are presented. The formations of the desired structures were validated using Atomic Force Microscopy (AFM) imagery. Five 3×4 DNA networks were successfully constructed using combinatorics of these five distinct DNA heterogeneous shapes. Our findings revealed that the construction of DNA supra-structures could be achieved using a more natural-like orchestration as compared to the rigid and restrictive conventional approaches adopted previously.
  17. Regulation of Glycine Cleavage and Detoxification by a Highly Conserved Glycine Riboswitch in Burkholderia spp
    Munyati-Othman N, Appasamy SD, Damiri N, Emrizal R, Alipiah NM, Ramlan EI, et al.
    Curr Microbiol, 2021 Aug;78(8):2943-2955.
    PMID: 34076709 DOI: 10.1007/s00284-021-02550-5
    The glycine riboswitch is a known regulatory element that is unique in having two aptamers that are joined by a linker region. In this study, we investigated a glycine riboswitch located in the 5' untranslated region of a glycine cleavage system homolog (gcvTHP) in Burkholderia spp. Structure prediction using the sequence generated a model with a glycine binding pocket composed of base-triple interactions (G62-A64-A86 and G65-U84-C85) that are supported by A/G minor interactions (A17-C60-G88 and G16-C61-G87, respectively) and two ribose-zipper motifs (C11-G12 interacting with A248-A247 and C153-U154 interacting with A79-A78) which had not been previously reported. The capacity of the riboswitch to bind to glycine was experimentally validated by native gel assays and the crucial role of interactions that make up the glycine binding pocket were proven by mutations of A17U and G16C which resulted in conformational differences that may lead to dysfunction. Using glycine supplemented minimal media, we were able to prove that the expression of the gcvTHP genes found downstream of the riboswitch responded to the glycine concentrations introduced thus confirming the role of this highly conserved Burkholderia riboswitch and its associated genes as a putative glycine detoxification system in Burkholderia spp.
  18. Fulltext Identification of sRNA mediated responses to nutrient depletion in Burkholderia pseudomallei
    Mohd-Padil H, Damiri N, Sulaiman S, Chai SF, Nathan S, Firdaus-Raih M
    Sci Rep, 2017 12 07;7(1):17173.
    PMID: 29215024 DOI: 10.1038/s41598-017-17356-4
    The Burkholderia genus includes many species that are known to survive in diverse environmental conditions including low nutrient environments. One species, Burkholderia pseudomallei is a versatile pathogen that can survive in a wide range of hosts and environmental conditions. In this study, we investigated how a nutrient depleted growth environment evokes sRNA mediated responses by B. pseudomallei. Computationally predicted B. pseudomallei D286 sRNAs were mapped to RNA-sequencing data for cultures grown under two conditions: (1) BHIB as a nutrient rich media reference environment and (2) M9 media as a nutrient depleted stress environment. The sRNAs were further selected to identify potentially cis-encoded systems by investigating their possible interactions with their flanking genes. The mappings of predicted sRNA genes and interactions analysis to their flanking genes identified 12 sRNA candidates that may possibly have cis-acting regulatory roles that are associated to a nutrient depleted growth environment. Our approach can be used for identifying novel sRNA genes and their possible role as cis-mediated regulatory systems.
  19. Fulltext Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei
    Nyanasegran PK, Nathan S, Firdaus-Raih M, Muhammad NAN, Ng CL
    J Microbiol Biotechnol, 2023 Jan 28;33(1):15-27.
    PMID: 36451302 DOI: 10.4014/jmb.2207.07032
    The incidence of melioidosis cases caused by the gram-negative pathogen Burkholderia pseudomallei (BP) is seeing an increasing trend that has spread beyond its previously known endemic regions. Biofilms produced by BP have been associated with antimicrobial therapy limitation and relapse melioidosis, thus making it urgently necessary to understand the mechanisms of biofilm formation and their role in BP biology. Microbial cells aggregate and enclose within a self-produced matrix of extracellular polymeric substances (EPSs) to form biofilm. The transition mechanism of bacterial cells from planktonic state to initiate biofilm formation, which involves the formation of surface attachment microcolonies and the maturation of the biofilm matrix, is a dynamic and complex process. Despite the emerging findings on the biofilm formation process, systemic knowledge on the molecular mechanisms of biofilm formation in BP remains fractured. This review provides insights into the signaling systems, matrix composition, and the biosynthesis regulation of EPSs (exopolysaccharide, eDNA and proteins) that facilitate the formation of biofilms in order to present an overview of our current knowledge and the questions that remain regarding BP biofilms.
  20. Fulltext GrAfSS: a webserver for substructure similarity searching and comparisons in the structures of proteins and RNA
    Ghani NSA, Emrizal R, Moffit SM, Hamdani HY, Ramlan EI, Firdaus-Raih M
    Nucleic Acids Res, 2022 Jul 05;50(W1):W375-W383.
    PMID: 35639505 DOI: 10.1093/nar/gkac402
    The GrAfSS (Graph theoretical Applications for Substructure Searching) webserver is a platform to search for three-dimensional substructures of: (i) amino acid side chains in protein structures; and (ii) base arrangements in RNA structures. The webserver interfaces the functions of five different graph theoretical algorithms - ASSAM, SPRITE, IMAAAGINE, NASSAM and COGNAC - into a single substructure searching suite. Users will be able to identify whether a three-dimensional (3D) arrangement of interest, such as a ligand binding site or 3D motif, observed in a protein or RNA structure can be found in other structures available in the Protein Data Bank (PDB). The webserver also allows users to determine whether a protein or RNA structure of interest contains substructural arrangements that are similar to known motifs or 3D arrangements. These capabilities allow for the functional annotation of new structures that were either experimentally determined or computationally generated (such as the coordinates generated by AlphaFold2) and can provide further insights into the diversity or conservation of functional mechanisms of structures in the PDB. The computed substructural superpositions are visualized using integrated NGL viewers. The GrAfSS server is available at http://mfrlab.org/grafss/.
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