Displaying publications 1 - 20 of 126 in total

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  1. Lam MQ, Nik Mut NN, Thevarajoo S, Chen SJ, Selvaratnam C, Hussin H, et al.
    3 Biotech, 2018 Feb;8(2):104.
    PMID: 29404232 DOI: 10.1007/s13205-018-1133-2
    A halophilic bacterium, Virgibacillus sp. strain CD6, was isolated from salted fish and its extracellular protease was characterized. Protease production was found to be highest when yeast extract was used as nitrogen source for growth. The protease exhibited stability at wide range of salt concentration (0-12.5%, w/v), temperatures (20-60 °C), and pH (4-10) with maximum activity at 10.0% (w/v) NaCl, 60 °C, pH 7 and 10, indicating its polyextremophilicity. The protease activity was enhanced in the presence of Mg2+, Mn2+, Cd2+, and Al3+ (107-122% relative activity), and with retention of activity > 80% for all of other metal ions examined (K+, Ca2+, Cu2+, Co2+, Ni2+, Zn2+, and Fe3+). Both PMSF and EDTA inhibited protease activity, denoting serine protease and metalloprotease properties, respectively. High stability (> 70%) was demonstrated in the presence of organic solvents and detergent constituents, and the extracellular protease from strain CD6 was also found to be compatible in commercial detergents. Proteinaceous stain removal efficacy revealed that crude protease of strain CD6 could significantly enhance the performance of commercial detergent. The protease from Virgibacillus sp. strain CD6 could serve as a promising alternative for various applications, especially in detergent industry.
    Matched MeSH terms: Serine Endopeptidases
  2. Gertsik N, Chau DM, Li YM
    ACS Chem. Biol., 2015 Aug 21;10(8):1925-31.
    PMID: 26030233 DOI: 10.1021/acschembio.5b00321
    γ-Secretase inhibitors (GSIs) and modulators (GSMs) are at the frontline of cancer and Alzheimer's disease research, respectively. While both are therapeutically promising, not much is known about their interactions with proteins other than γ-secretase. Signal peptide peptidase (SPP), like γ-secretase, is a multispan transmembrane aspartyl protease that catalyzes regulated intramembrane proteolysis. We used active site-directed photophore walking probes to study the effects of different GSIs and GSMs on the active sites of γ-secretase and SPP and found that nontransition state GSIs inhibit labeling of γ-secretase by activity-based probes but enhance labeling of SPP. The opposite is true of GSMs, which have little effect on the labeling of γ-secretase but diminish labeling of SPP. These results demonstrate that GSIs and GSMs are altering the structure of not only γ-secretase but also SPP, leading to potential changes in enzyme activity and specificity that may impact the clinical outcomes of these molecules.
    Matched MeSH terms: Aspartic Acid Endopeptidases/chemistry*
  3. Alhelli AM, Mohammed NK, Khalil ES, Hussin ASM
    AMB Express, 2021 Mar 22;11(1):45.
    PMID: 33751265 DOI: 10.1186/s13568-021-01205-9
    Cheddar cheese proteolysis were accelerated employing Penicillium candidum PCA1/TT031 protease into cheese curd. In the present study, several of the significant factors such as protease purification factor (PF), protease concentration and ripening time were optimized via the response surface methodology (RSM). The ideal accelerated Cheddar cheese environment consisted of 3.12 PF, 0.01% (v/v) protease concentration and 0.6/3 months ripening time at 10 °C. The RSM models was verified to be the most proper methodology for the maintain of chosen Cheddar cheese. Under this experimental environment, the pH, acid degree value (ADV), moisture, water activity (aw), soluble nitrogen (SN)%, fat and overall acceptability were found to be 5.4, 6.6, 35%, 0.9348, 18.8%, 34% and 13.6, respectively of ideal Cheddar cheese. Furthermore, the predicted and experimental results were in significant agreement, which confirmed the validity and reliability of the suggested method. In spite of the difference between the ideal and commercial Cheddar cheese in the concentration of some of amino acids and free fatty acids, the sensory evaluation did not show any significant difference in aroma profile between them.
    Matched MeSH terms: Endopeptidases
  4. Hempolchom C, Reamtong O, Sookrung N, Srisuka W, Sakolvaree Y, Chaicumpa W, et al.
    Acta Trop, 2019 Jun;194:82-88.
    PMID: 30922801 DOI: 10.1016/j.actatropica.2019.03.026
    Although several studies have reported pharmacological and immunological activity, as well as the role of black flies in transmitting pathogens to vertebrate hosts through salivary glands (SG) during blood feeding, SG proteomes of the anthropophilic black flies in Thailand have never been reported. Therefore, this study determined the SG proteomes of female S. nigrogilvum and S. nodosum. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional (2-DE) gels containing separated SG proteins of individual species were subjected to liquid chromatography-tandem mass spectrometry (LCMS/MS) and an orthologous protein search from eukaryotic organism, nematocera and simuliidae databases for total protein identification. SDS-PAGE and protein staining revealed at least 13 and 9 major protein bands in the SGs of female S. nigrogilvum and S. nodosum, respectively, as well as several minor ones. The 2-DE demonstrated a total of 56 and 41 protein spots for S. nigrogilvum and S. nodosum, respectively. Most of the proteins obtained in both species were enzymes involved in blood feeding, including proteases, apyrases, hyaluronidases, aminopeptidase and elastase. The results obtained in this study provided a new body of knowledge for a better understanding on the role of salivary gland proteins in these black fly species in Thailand.
    Matched MeSH terms: Endopeptidases
  5. Hagen RM, Adamo P, Karamat S, Oxley J, Aning JJ, Gillatt D, et al.
    Am J Clin Pathol, 2014 Oct;142(4):533-40.
    PMID: 25239421 DOI: 10.1309/AJCPH88QHXARISUP
    The proto-oncogene ETS-related gene (ERG) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses.
    Matched MeSH terms: Serine Endopeptidases/genetics*; Serine Endopeptidases/metabolism
  6. Lorrine OE, Rahman RNZRA, Joo Shun T, Salleh AB, Oslan SN
    Anal Biochem, 2023 May 01;668:115092.
    PMID: 36889624 DOI: 10.1016/j.ab.2023.115092
    In eukaryotes, serine proteases are cellular localized hydrolases reported to regulate essential biological reactions. Improved industrial applications of proteins are aided by prediction and analysis of their 3-dimensional structures (3D). A serine protease was identified from CTG-clade yeast Meyerozyma guilliermondii strain SO and its 3D structure as well as its catalytic attributes have not been fully understood yet, thus we seek to report on the catalytic mechanism of M. guilliermondii strain SO MgPRB1 using substrate PMSF via in silico docking as well as its stability by way of disulfide bonds formation. Herein, bioinformatics tools and techniques were used to predict, validate and analyze the possible changes of CUG ambiguity (if any) in strain SO using template PDB ID: 3F7O. Structural assessments confirmed the classic catalytic triad Asp305, His337, and Ser499. Superimposition of MgPRB1 and template 3F7O structures revealed the unlinked cysteine residues between Cys341, Cys440, Cys471 and Cys506 of MgPRB1 compared to template 3F7O with two disulfide bonds formation, which confers structural stability. In conclusion, serine protease structure from strain SO was successfully predicted and studies towards understanding at the molecular level may be undertaken for its potential applications in the degradation of peptide bonds.
    Matched MeSH terms: Serine Endopeptidases
  7. Tan CW, Sam IC, Chong WL, Lee VS, Chan YF
    Antiviral Res, 2017 07;143:186-194.
    PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017
    Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
    Matched MeSH terms: Serine Endopeptidases/drug effects; Serine Endopeptidases/chemistry
  8. Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

    Matched MeSH terms: Aspartic Acid Endopeptidases/antagonists & inhibitors*
  9. Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R
    BMC Infect Dis, 2012;12:314.
    PMID: 23171075 DOI: 10.1186/1471-2334-12-314
    Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not available at the moment. In this study, we report retrocyclin-1 (RC-1) production in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro.
    Matched MeSH terms: Endopeptidases/metabolism*
  10. Law WY, Asaruddin MR, Bhawani SA, Mohamad S
    BMC Res Notes, 2020 Nov 11;13(1):527.
    PMID: 33176880 DOI: 10.1186/s13104-020-05379-6
    OBJECTIVES: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions.

    RESULTS: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent MPro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant MPro inhibition.

    Matched MeSH terms: Cysteine Endopeptidases
  11. Tham HY, Song AA, Yusoff K, Tan GH
    Biotechniques, 2020 09;69(3):161-170.
    PMID: 32787565 DOI: 10.2144/btn-2020-0034
    Endolysins have been studied intensively as an alternative to antibiotics. In this study, endolysin derived from a phage which infects methicillin-resistant Staphylococcus aureus (MRSA) was cloned and expressed in Escherichia coli pET28a. Initially, the endolysin was cloned using BamHI/XhoI, resulting in expression of a recombinant endolysin which was expressed in inclusion bodies. While solubilization was successful, the protein remained nonfunctional. Recloning the endolysin using NcoI/XhoI resulted in expression of soluble and functional proteins at 18°C. The endolysin was able to form halo zones on MRSA plates and showed a reduction in turbidity of MRSA growth. Therefore, cloning strategies should be chosen carefully even in an established expression system as they could greatly affect the functionality of the expressed protein.
    Matched MeSH terms: Endopeptidases/genetics*
  12. Scaramozzino N, Crance JM, Drouet C, Roebuck JP, Drouet E, Jouan A, et al.
    Biochem Biophys Res Commun, 2002 May 31;294(1):16-22.
    PMID: 12054734
    Langat (LGT) virus, initially isolated in 1956 from ticks in Malaysia, is a naturally occurring nonpathogenic virus with a very close antigenicity to the highly pathogenic tick-borne encephalitis (TBE) Western subtype virus and TBE Far Eastern subtype virus. NS3, the second largest viral protein of LGT virus, is highly conserved among flaviviruses and contains a characteristic protease moiety (NS3 pro). NS3 pro represents an attractive target for anti-protease molecules against TBE virus. We report herein a purification method specially designed for NS3 pro of LGT using a strategy for proper refolding coupled with the enzymatic characterisation of the protein. Different p-nitroanilide substrates, defined on canonic sequences for their susceptibility to Ser-protease, were applied to the proteolytic assays of the protein. The highest values were obtained from substrates containing an Arg or Lys (amino acid) residue at the P1 position. This purification method will facilitate the future development of reliable testing procedures for anti-proteases directed to NS3 proteins.
    Matched MeSH terms: Serine Endopeptidases/metabolism*
  13. Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R
    Biomed Rep, 2016 Sep;5(3):283-288.
    PMID: 27602208
    Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain.
    Matched MeSH terms: Endopeptidases
  14. Ismail N, Ismail M, Azmi NH, Bakar MFA, Yida Z, Abdullah MA, et al.
    Biomed Pharmacother, 2017 Nov;95:780-788.
    PMID: 28892789 DOI: 10.1016/j.biopha.2017.08.074
    Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue.
    Matched MeSH terms: Aspartic Acid Endopeptidases/metabolism*
  15. Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Rahman NA
    Bioorg Med Chem Lett, 2006 Jun 15;16(12):3337-40.
    PMID: 16621533
    Boesenbergia rotunda (L.) cyclohexenyl chalcone derivatives, 4-hydroxypanduratin A and panduratin A, showed good competitive inhibitory activities towards dengue 2 virus NS3 protease with the Ki values of 21 and 25 microM, respectively, whilst those of pinostrobin and cardamonin were observed to be non-competitive. NMR and GCMS spectroscopic data formed the basis of assignment of structures of the six compounds isolated.
    Matched MeSH terms: Serine Endopeptidases/metabolism*
  16. Halmi, M.I.E., Khayat, M.E., Rahman, M.F.A., Gunasekaran, B., Masdor, N.A.
    MyJurnal
    In this work, a temporal monitoring work for heavy metals from an effluent discharge point in
    the Juru Industrial Estate was carried out using the protease extracted from garlic (Allium
    sativum) as the principal bioassay system. casein-Coomassie-dye binding assay method has
    utilized this purpose. The periodic sampling results for one day of a location in the Juru
    Industrial Estate showed temporal variation of copper concentration coinciding with garlic
    protease inhibition with the highest concentrations of copper occurring between 12.00 and 16.00
    hours of between 3 and 3.5 mg/L copper. The crude proteases extracted from Allium sativum
    successfully detect temporal variation of copper form this location. In conclusion, this assay
    method has the potential to be a rapid, sensitive, and economic inhibitive assay for the largescale
    biomonitoring works for the heavy metal copper from this area.
    Matched MeSH terms: Endopeptidases
  17. Gunasekaran, B., Johari, W.L.W., Wasoh, M.H., Masdor, N.A., Shukor, M.Y.
    MyJurnal
    Heavy metals pollution has become a great threat to the world. Since instrumental methods are
    expensive and need skilled technician, a simple and fast method is needed to determine the
    presence of heavy metals in the environment. In this work, a preliminary study was carried out
    on the applicability of various local plants as a source of protease for the future development of
    the inhibitive enzyme assay for heavy-metals. The crude proteases preparation was assayed using
    casein as a substrate in conjunction with the Coomassie dye-binding assay. The crude protease
    from the kesinai plant was found to be the most potent plant protease. The crude enzyme
    exhibited broad temperature and pH ranges for activity and will be developed in the future as a
    potential inhibitive assay for heavy metals.
    Matched MeSH terms: Endopeptidases
  18. Heh CH, Othman R, Buckle MJ, Sharifuddin Y, Yusof R, Rahman NA
    Chem Biol Drug Des, 2013 Jul;82(1):1-11.
    PMID: 23421589 DOI: 10.1111/cbdd.12122
    Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.
    Matched MeSH terms: Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism
  19. Tan NH, Ponnudurai G
    Comp. Biochem. Physiol., B, 1991;99(2):351-4.
    PMID: 1764914
    1. The protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, procoagulant, anticoagulant and hemorrhagic activities of ten samples of venoms from seven taxa of sea snakes were examined. 2. The results show that venoms of sea snakes of both subfamilies of Hydrophiinae and Laticaudinae are characterized by a very low level of enzymatic activities, except phospholipase A activity and, for some species, hyaluronidase activity. 3. Because of the low levels of enzymatic activities and the total lack of procoagulant and hemorrhagic activities, venom biological properties are not useful for the differentiation of species of sea snakes. Nevertheless, the unusually low levels of enzymatic activities of sea snake venoms may be used to distinguish sea snake venoms from other elapid or viperid venoms.
    Matched MeSH terms: Endopeptidases/metabolism
  20. Tan NH, Armugam A, Tan CS
    Comp. Biochem. Physiol., B, 1989;93(4):757-62.
    PMID: 2553329
    1. The lethalities, anticoagulant effects, hermorrhagic, thrombin-like enzyme, hyaluronidase, protease, arginine ester hydrolase, 5'-nucleotidase, L-amino acid oxidase, alkaline phosphomonoesterase, phosphodiesterase and phospholipase A activities of twenty-three samples of venoms from twelve species of Asian lance-headed pit vipers (genus Trimeresurus) were examined. 2. The results indicate that notwithstanding individual variations in venom properties, the differences in biological properties of the Trimeresurus venoms can be used for the differentiation of venoms from different species of Trimeresurus. 3. The results also suggest that differences in the biological properties of snake venoms are useful parameters in the classification of snake species. 4. Our results indicate that venoms from the species T. okinavensis exhibited biological properties markedly different from other Trimeresurus venoms examined. This observation supports the recently proposed reclassification of T. okinavensis as a member of the genus Ovophis, rather than the genus Trimeresurus.
    Matched MeSH terms: Endopeptidases/metabolism
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