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Characterisation of a catalytic triad and reaction selectivity in the dual mechanism of the catalyse hydride transfer in xylitol phosphate dehydrogenase

Razali SA, Shamsir MS

J Mol Graph Model, 2020 06;97:107548.
PMID: 32023508 DOI: 10.1016/j.jmgm.2020.107548

Xylitol is a high-value low-calorie sweetener used as sugar substitute in food and pharmaceutical industry. Xylitol phosphate dehydrogenase (XPDH) catalyses the conversion of d-xylulose 5-phosphate (XU5P) and d-ribulose 5-phosphate (RU5P) to xylitol and ribitol respectively in the presence of nicotinamide adenine dinucleotide hydride (NADH). Although these enzymes have been shown to produce xylitol and ribitol, there is an incomplete understanding of the mechanism of the catalytic events of these reactions and the detailed mechanism has yet to be elucidated. The main goal of this work is to analyse the conformational changes of XPDH-bound ligands such as zinc, NADH, XU5P, and RU5P to elucidate the key amino acids involved in the substrate binding. In silico modelling, comparative molecular dynamics simulations, interaction analysis and conformational study were carried out on three XPDH enzymes of the Medium-chain dehydrogenase (MDR) family in order to elucidate the atomistic details of conformational transition, especially on the open and closed state of XPDH. The analysis also revealed the possible mechanism of substrate specificity that are responsible in the catalyse hydride transfer are the residues His58 and Ser39 which would act as the proton donor for reduction of XU5P and RU5P respectively. The structural comparison and MD simulations displayed a significant difference in the conformational dynamics of the catalytic and coenzyme loops between Apo and XPDH-complexes and highlight the contribution of newly found triad residues. This study would assist future mutagenesis study and enzyme modification work to increase the catalysis efficiency of xylitol production in the industry.
Fulltext Data on PCR primer design for glucose 6-phosphate dehydrogenase gene and the effects of dietary carbohydrate levels on its expression in the liver of Malaysian mahseer (Tor tambroides)

Ishak SD, Razali SA, Kamarudin MS, Abol-Munafi AB

Data Brief, 2020 Aug;31:105916.
PMID: 32642522 DOI: 10.1016/j.dib.2020.105916

The enzyme glucose-6-phosphate dehydrogenase (G6PD) catalyses the metabolite glucose-6-phosphate in producing NADPH during the first phase of pentose-phosphate pathway thus provides reducing power to all cells for cellular growth, antioxidant defence, and biosynthetic reactions in all living organism. The deliberate inclusion of starch as carbohydrate source in commercial feed however may affect the G6PD hepatic activity in cultured fish. We designed a set of primers to target G6PD gene in the popular Malaysian aquaculture species, Tor tambroides. For this dataset, the molecular characteristics of obtained T. tambroides G6PD (TtG6PD) nucleotide sequence was analysed using multiple alignments and phylogenetic analyses of the deduced amino acids. The set of primers obtained were then used in a study to evaluate the effect of different dietary carbohydrate inclusion levels on the hepatic TtG6PD mRNA expression of the T. tambroides fingerlings. Four groups of fish were given a dietary treatment of 15%, 20%, 25% and 30% starch at the optimal inclusion level of 23.4% for 10 weeks. The TtG6PD mRNA transcripts were measured using real-time-PCR assays and its expression normalized against β-actin, which acts as the internal control gene. This article provides supportive data in relation between hepatic TtG6PD mRNA gene expression in T. tambroides and how it is influenced by its dietary carbohydrate intake. These data will also assist in further nutritional genomic studies of carbohydrate and energy utilization for all species in the mahseer family.
Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins

Mohamad Rosdi MN, Mohd Arif S, Abu Bakar MH, Razali SA, Mohamed Zulkifli R, Ya'akob H

Apoptosis, 2018 01;23(1):27-40.
PMID: 29204721 DOI: 10.1007/s10495-017-1434-7

Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.
Synthesis, anti-amoebic activity and molecular docking simulation of eugenol derivatives against Acanthamoeba sp

Zamli KM, Hashim F, Razali SA, Yusoff HM, Mohamad H, Abdullah F, et al.

Saudi Pharm J, 2023 Sep;31(9):101703.
PMID: 37546528 DOI: 10.1016/j.jsps.2023.101703

Amoebae of the genus Acanthamoeba can cause diseases such as amoebic keratitis and granulomatous amoebic encephalitis. Until now, treatment options for these diseases have not been fully effective and have several drawbacks. Therefore, research into new drugs is needed for more effective treatment of Acanthamoeba infections. Eugenol, a phenolic aromatic compound mainly derived from cloves, has a variety of pharmaceutical properties. In this study, nine eugenol derivatives (K1-K9), consisting of five new and four known compounds, were synthesized and screened for their antiamoebic properties against Acanthamoeba sp. The structure of these compounds was characterized spectroscopically by Fourier transform infrared (FTIR), Ultraviolet-Visible (UV-Vis), 1H and 13C Nuclear Magnetic Resonance (NMR) and mass spectrometer (MS). The derived molecules were screened for antiamoebic activity by determining IC50 values based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and observation of amoeba morphological changes by light and fluorescence microscopy. Most of the tested compounds possessed strong to moderate cytotoxic effects against trophozoite cells with IC50 values ranging from 0.61 to 24.83 μg/mL. Observation of amoebae morphology by light microscopy showed that the compounds caused the transformed cells to be roundish and reduced in size. Furthermore, fluorescence microscopy observation using acridine orange (AO) and propidium iodide (PI) (AO/PI) staining showed that the cells have damaged membranes by displaying a green cytoplasm with orange-stained lysosomes. Acidification of the lysosomal structure indicated disruption of the internal structure of Acanthamoeba cells when treated with eugenol derivatives. The observed biological results were also confirmed by interaction simulations based on molecular docking between eugenol derivatives and Acanthamoeba profilin. These interactions could affect the actin-binding ability of the protein, disrupting the shape and mobility of Acanthamoeba. The overall results of this study demonstrate that eugenol derivatives can be considered as potential drugs against infections caused by Acanthamoeba.
Fulltext Molecular docking and simulation studies of Chloroquine, Rimantadine and CAP-1 as potential repurposed antivirals for decapod iridescent virus 1 (DIV1)

Azemin WA, Ishak NF, Saedin MAA, Shamsir MS, Razali SA

Fish Shellfish Immunol Rep, 2023 Dec 15;5:100120.
PMID: 37854946 DOI: 10.1016/j.fsirep.2023.100120

Drug repurposing is a methodology of identifying new therapeutic use for existing drugs. It is a highly efficient, time and cost-saving strategy that offers an alternative approach to the traditional drug discovery process. Past in-silico studies involving molecular docking have been successful in identifying potential repurposed drugs for the various treatment of diseases including aquaculture diseases. The emerging shrimp hemocyte iridescent virus (SHIV) or Decapod iridescent virus 1 (DIV1) is a viral pathogen that causes severe disease and high mortality (80 %) in farmed shrimps caused serious economic losses and presents a new threat to the shrimp farming industry. Therefore, effective antiviral drugs are critically needed to control DIV1 infections. The aim of this study is to investigate the interaction of potential existing antiviral drugs, Chloroquine, Rimantadine, and CAP-1 with DIV1 major capsid protein (MCP) with the intention of exploring the potential of drug repurposing. The interaction of the DIV1 MCP and three antivirals were characterised and analysed using molecular docking and molecular dynamics simulation. The results showed that CAP-1 is a more promising candidate against DIV1 with the lowest binding energy of -8.46 kcal/mol and is more stable compared to others. We speculate that CAP-1 binding may induce the conformational changes in the DIV1 MCP structure by phosphorylating multiple residues (His123, Tyr162, and Thr395) and ultimately block the viral assembly and maturation of DIV1 MCP. To the best of our knowledge, this is the first report regarding the structural characterisation of DIV1 MCP docked with repurposing drugs.
Fulltext Muntingia calabura Leaves Mediated Green Synthesis of CuO Nanorods: Exploiting Phytochemicals for Unique Morphology

Selvanathan V, Aminuzzaman M, Tey LH, Razali SA, Althubeiti K, Alkhammash HI, et al.

Materials (Basel), 2021 Oct 25;14(21).
PMID: 34771914 DOI: 10.3390/ma14216379

In this study, phytochemical assisted nanoparticle synthesis was performed using Muntingia calabura leaf extracts to produce copper oxide nanoparticles (CuO NPs) with interesting morphology. Scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis of the biosynthesized CuO NPs reveal formation of distinct, homogeneous, and uniform sized CuO nanorods structure with thickness and length of around 23 nm and 79 nm, respectively. Based on Fourier-transform infrared (FTIR) analysis, the unique combinations of secondary metabolites such as flavonoid and polyphenols in the plant extract are deduced to be effective capping agents to produce nanoparticles with unique morphologies similar to conventional chemical synthesis. X-ray diffraction (XRD) analysis verified the monoclinical, crystalline structure of the CuO NPs. The phase purity and chemical identity of the product was consolidated via X-Ray photoelectron spectroscopy (XPS) and Raman spectroscopic data which indicate the formation of a single phase CuO without the presence of other impurities. The direct and indirect optical band gap energies of the CuO nanorods were recorded to be 3.65 eV and 1.42 eV.
Fulltext Applications of Next-Generation Sequencing Technologies and Computational Tools in Molecular Evolution and Aquatic Animals Conservation Studies: A Short Review

Tan MP, Wong LL, Razali SA, Afiqah-Aleng N, Mohd Nor SA, Sung YY, et al.

Evol Bioinform Online, 2019;15:1176934319892284.
PMID: 31839703 DOI: 10.1177/1176934319892284

Aquatic ecosystems that form major biodiversity hotspots are critically threatened due to environmental and anthropogenic stressors. We believe that, in this genomic era, computational methods can be applied to promote aquatic biodiversity conservation by addressing questions related to the evolutionary history of aquatic organisms at the molecular level. However, huge amounts of genomics data generated can only be discerned through the use of bioinformatics. Here, we examine the applications of next-generation sequencing technologies and bioinformatics tools to study the molecular evolution of aquatic animals and discuss the current challenges and future perspectives of using bioinformatics toward aquatic animal conservation efforts.
Fulltext Computationally Designed Anti-LuxP DNA Aptamer Suppressed Flagellar Assembly- and Quorum Sensing-Related Gene Expression in Vibrio parahaemolyticus

Yusof NAM, Razali SA, Mohd Padzil A, Lau BYC, Baharum SN, Nor Muhammad NA, et al.

Biology (Basel), 2022 Nov 01;11(11).
PMID: 36358301 DOI: 10.3390/biology11111600

(1) Background: Quorum sensing (QS) is the chemical communication between bacteria that sense chemical signals in the bacterial population to control phenotypic changes through the regulation of gene expression. The inhibition of QS has various potential applications, particularly in the prevention of bacterial infection. QS can be inhibited by targeting the LuxP, a periplasmic receptor protein that is involved in the sensing of the QS signaling molecule known as the autoinducer 2 (AI-2). The sensing of AI-2 by LuxP transduces the chemical information through the inner membrane sensor kinase LuxQ protein and activates the QS cascade. (2) Methods: An in silico approach was applied to design DNA aptamers against LuxP in this study. A method combining molecular docking and molecular dynamics simulations was used to select the oligonucleotides that bind to LuxP, which were then further characterized using isothermal titration calorimetry. Subsequently, the bioactivity of the selected aptamer was examined through comparative transcriptome analysis. (3) Results: Two aptamer candidates were identified from the ITC, which have the lowest dissociation constants (Kd) of 0.2 and 0.5 micromolar. The aptamer with the lowest Kd demonstrated QS suppression and down-regulated the flagellar-assembly-related gene expression. (4) Conclusions: This study developed an in silico approach to design an aptamer that possesses anti-QS properties.
Fulltext Clinical students' reflections on the preclinical anatomy learning experience

Syed Abd Halim SA, Yusoff MSB, Yaman MN, Razali SA, Tengku Muda TFM, Ramli RR, et al.

J Taibah Univ Med Sci, 2023 Aug;18(4):757-770.
PMID: 36852241 DOI: 10.1016/j.jtumed.2022.12.007

OBJECTIVES: Anatomy is a fundamental pillar of medical knowledge that bridges basic medical science knowledge and clinical practice. However, integrated modern medical curricula have reduced the anatomy teaching content, and cadaveric dissection is no longer conducted. Medical graduates who lack anatomy knowledge are anticipated to be inadequately equipped for safe clinical practice. This study was aimed at exploring clinical year students' experiences regarding their anatomy learning during the preclinical phase in Malaysian medical schools. The findings reflect how the students' preclinical anatomy training prepared them for their clinical years of study.
METHODS: A qualitative phenomenology study using the focus group discussion method was conducted on 30 final-year students from four public universities. Four focus group discussion sessions were conducted, and students' responses were transcribed and converted to electronic formats. The transcripts were analyzed thematically with ATLAS.ti software.
RESULTS: The first-cycle coding of the text analysis generated 157 open codes based on the phrases used by the participants. The subsequent coding cycle produced 16 axial codes-groups of open codes with similar features. During the final coding cycle, the content and interrelations between the axial codes were categorized into six codes: (1) preclinical anatomy learning experience, (2) anatomy content and teaching, (3) anatomy-related competency, (4) the importance of anatomy knowledge in clinical practice, (5) the importance of early exposure to applied clinical anatomy, and (6) suggestions for future anatomy education.
CONCLUSIONS: The six identified themes reflected students' perceptions of their anatomy learning experience, the challenges that they faced during their preclinical years, and their opinions regarding the anatomy knowledge and skills that are functionally relevant during the clinical years. Their responses also echoed the need to improve anatomy teaching and learning, thereby emphasizing the importance of early clinical integration and application.