Displaying publications 121 - 140 of 200 in total

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  1. Fulltext Cloning, expression, purification, crystallization and X-ray crystallographic analysis of recombinant human C1ORF123 protein
    Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Ho KL, Teh AH, Waterman J, et al.
    Acta Crystallogr F Struct Biol Commun, 2016 Mar;72(Pt 3):207-13.
    PMID: 26919524 DOI: 10.1107/S2053230X16002016
    C1ORF123 is a human hypothetical protein found in open reading frame 123 of chromosome 1. The protein belongs to the DUF866 protein family comprising eukaryote-conserved proteins with unknown function. Recent proteomic and bioinformatic analyses identified the presence of C1ORF123 in brain, frontal cortex and synapses, as well as its involvement in endocrine function and polycystic ovary syndrome (PCOS), indicating the importance of its biological role. In order to provide a better understanding of the biological function of the human C1ORF123 protein, the characterization and analysis of recombinant C1ORF123 (rC1ORF123), including overexpression and purification, verification by mass spectrometry and a Western blot using anti-C1ORF123 antibodies, crystallization and X-ray diffraction analysis of the protein crystals, are reported here. The rC1ORF123 protein was crystallized by the hanging-drop vapor-diffusion method with a reservoir solution comprised of 20% PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M sodium citrate pH 6.5. The crystals diffracted to 1.9 Å resolution and belonged to an orthorhombic space group with unit-cell parameters a = 59.32, b = 65.35, c = 95.05 Å. The calculated Matthews coefficient (VM) value of 2.27 Å(3) Da(-1) suggests that there are two molecules per asymmetric unit, with an estimated solvent content of 45.7%.
    Matched MeSH terms: Crystallography, X-Ray
  2. Synthesis of a DNA-targeting nickel (II) complex with testosterone thiosemicarbazone which exhibits selective cytotoxicity towards human prostate cancer cells (LNCaP)
    Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Nov 5;150:360-72.
    PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095
    Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
    Matched MeSH terms: Crystallography, X-Ray
  3. Fulltext Crystal structure of Plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody
    Vulliez-Le Normand B, Faber BW, Saul FA, van der Eijk M, Thomas AW, Singh B, et al.
    PLoS One, 2015;10(4):e0123567.
    PMID: 25886591 DOI: 10.1371/journal.pone.0123567
    The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host's humoral response to AMA1.
    Matched MeSH terms: Crystallography, X-Ray
  4. Exhaustive study of the novel hyper alkalophil, thermostable, and chelator resistant metalloprotease
    Samie N, Haerian B, Muniandy S, Green D, Ashouri M
    Appl Biochem Biotechnol, 2015 Apr;175(7):3397-417.
    PMID: 25820296 DOI: 10.1007/s12010-015-1513-6
    Our newly discovered metalloprotease, designated as ALP NS12 was selected using gelatin agar plates with incubation at 100 °C. Subcloning of the fragments in to pUC118 to make E. coli HB101 (pPEMP01NS) with following two-step chromatography using diethylaminoethyl sepharose (DEAE-sepharose) and Sephadex G-100 columns to purify 97-kDa expressed enzyme was performed. Although activity of immobilized ALP NS12 on glass surface was established at temperatures between 70 and 120 °C and pH ranges 4.0-13.0, the optimum temperature and pH were achieved at 100 °C and 11.0, respectively. Enhancement of enzyme activity was obtained in the presence of 5 mM MnCl2 (91 %), CaCl2 (357 %), FeCl2 (175 %), MgCl2 (94 %), ZnCl2 (412 %), NiCl (86 %), NaCl (239 %), and Na-sulfate (81 %) while inhibition was observed with EDTA (5 mM), PMSF (3 mM), urea (8 M), and SDS (1 %) at 65, 37, 33, and 42 %, respectively. Consequently, the enzyme was well analyzed using crystallography and protein modeling. ALP NS12 can be applied in industrial processes at extreme temperatures and under highly basic conditions, chelators, and detergents.
    Matched MeSH terms: Crystallography, X-Ray
  5. Fulltext Reductive evolution in outer membrane protein biogenesis has not compromised cell surface complexity in Helicobacter pylori
    Webb CT, Chandrapala D, Oslan SN, Bamert RS, Grinter RD, Dunstan RA, et al.
    Microbiologyopen, 2017 12;6(6).
    PMID: 29055967 DOI: 10.1002/mbo3.513
    Helicobacter pylori is a gram-negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host-pathogen interactions mediated by Helicobacter-specific proteins in the bacterial outer membrane. These outer membrane proteins (OMPs) are anchored to the cell surface via a C-terminal β-barrel domain, which requires their assembly by the β-barrel assembly machinery (BAM). Here we have assessed the complexity of the OMP C-terminal β-barrel domains employed by H. pylori, and characterized the H. pyloriBAM complex. Around 50 Helicobacter-specific OMPs were assessed with predictive structural algorithms. The data suggest that H. pylori utilizes a unique β-barrel architecture that might constitute H. pylori-specific Type V secretions system. The structural and functional diversity in these proteins is encompassed by their extramembrane domains. Bioinformatic and biochemical characterization suggests that the low β-barrel-complexity requires only minimalist assembly machinery. The H. pylori proteins BamA and BamD associate to form a BAM complex, with features of BamA enabling an oligomerization that might represent a mechanism by which a minimalist BAM complex forms a larger, sophisticated machinery capable of servicing the outer membrane proteome of H. pylori.
    Matched MeSH terms: Crystallography, X-Ray
  6. Fulltext Synthesis, characterization, quantum chemical calculations and anticancer activity of a Schiff base NNOO chelate ligand and Pd(II) complex
    Ahmad N, Anouar EH, Tajuddin AM, Ramasamy K, Yamin BM, Bahron H
    PLoS One, 2020;15(4):e0231147.
    PMID: 32287324 DOI: 10.1371/journal.pone.0231147
    This paper reports the synthesis, characterization, anticancer screening and quantum chemical calculation of a tetradentate Schiff base 2,2'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis- (azanylylidene))bis(methanylylidene))bis(4-fluorophenol) (L2F) and its Pd (II) complex (PdL2F). The compounds were characterized via UV-Visible, NMR, IR spectroscopy and single crystal x-ray diffraction. Density Functional Theory (DFT) and time-dependent DFT calculations in gas and solvent phases were carried out using B3LYP, B3P86, CAM-B3LYP and PBE0 hybrid functionals combined with LanL2DZ basis set. Complexation of L2F to form PdL2F was observed to cause a bathochromic shift of the maximum absorption bands of n-π* from 327 to 410 nm; an upfield shift for δ (HC = N) from 8.30 to 7.96 ppm and a decreased wavenumber for ν(C = N) from 1637 to 1616 cm-1. Overall, the UV-Vis, NMR and IR spectral data are relatively well reproduced through DFT and TD-DFT methods. L2F and PdL2F showed IC50 of 90.00 and 4.10 μg/mL, respectively, against human colorectal carcinoma (HCT116) cell lines, signifying increased anticancer activity upon complexation with Pd (II).
    Matched MeSH terms: Crystallography, X-Ray
  7. Factors affecting nucleolytic efficiency of some ternary metal complexes with DNA binding and recognition domains. Crystal and molecular structure of Zn(phen)(edda)
    Seng HL, Ong HK, Rahman RN, Yamin BM, Tiekink ER, Tan KW, et al.
    J Inorg Biochem, 2008 Nov;102(11):1997-2011.
    PMID: 18778856 DOI: 10.1016/j.jinorgbio.2008.07.015
    The binding selectivity of the M(phen)(edda) (M=Cu, Co, Ni, Zn; phen=1,10-phenanthroline, edda=ethylenediaminediacetic acid) complexes towards ds(CG)(6), ds(AT)(6) and ds(CGCGAATTCGCG) B-form oligonucleotide duplexes were studied by CD spectroscopy and molecular modeling. The binding mode is intercalation and there is selectivity towards AT-sequence and stacking preference for A/A parallel or diagonal adjacent base steps in their intercalation. The nucleolytic properties of these complexes were investigated and the factors affecting the extent of cleavage were determined to be: concentration of complex, the nature of metal(II) ion, type of buffer, pH of buffer, incubation time, incubation temperature, and the presence of hydrogen peroxide or ascorbic acid as exogenous reagents. The fluorescence property of these complexes and its origin were also investigated. The crystal structure of the Zn(phen)(edda) complex is reported in which the zinc atom displays a distorted trans-N(4)O(2) octahedral geometry; the crystal packing features double layers of complex molecules held together by extensive hydrogen bonding that inter-digitate with adjacent double layers via pi...pi interactions between 1,10-phenanthroline residues. The structure is compared with that of the recently described copper(II) analogue and, with the latter, included in molecular modeling.
    Matched MeSH terms: Crystallography, X-Ray
  8. Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable apoptosis mediated by reactive oxygen species
    Basu Baul TS, Dutta D, Duthie A, Prasad R, Rana NK, Koch B, et al.
    J Inorg Biochem, 2017 08;173:79-92.
    PMID: 28505480 DOI: 10.1016/j.jinorgbio.2017.04.020
    The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3; isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR (1H,13C,119Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50value of 1.19 and 1.44μM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50value of 0.88μM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.
    Matched MeSH terms: Crystallography, X-Ray
  9. Docking Studies of Curcumin and Analogues with Various Phosphodiesterase 4 Subtypes
    Yi YX, Gaurav A, Akowuah GA
    Curr Drug Discov Technol, 2020;17(2):248-260.
    PMID: 30332967 DOI: 10.2174/1570163815666181017091655
    INTRODUCTION: The primary aim of this study is to understand the binding of curcumin and its analogues to different PDE4 subtypes and identify the role of PDE4 subtype inhibition in the anti-inflammatory property of curcumin. Docking analysis has been used to acquire the above mentioned structural information and this has been further used for designing of curcumin derivatives with better anti-inflammatory activity.

    MATERIALS AND METHODS: Curcumin and its analogues were subjected to docking using PDE4A, PDE4B, PDE4C and PDE4D as the targets. A data set comprising 18 analogues of curcumin, was used as ligands for docking of PDE4 subtypes. Curcumin was used as the standard for comparison. Docking was performed using AutoDock Vina 1.1.2 software integrated in LigandScout 4.1. During this process water molecules were removed from proteins, charges were added and receptor structures were minimised by applying suitable force fields. The docking scores were compared, and the selectivity of compounds for PDE4B over PDE4D was calculated as well.

    RESULTS: All curcumin analogues used in the study showed good binding affinity with all PDE4 subtypes, with evident selectivity towards PDE4B subtype. Analogue A11 provides the highest binding affinity among all ligands.

    CONCLUSION: Curcumin and analogues have moderate to strong affinity towards all PDE4 subtypes and have evident selectivity towards PDE4B. The Oxygen atom of the methoxy group plays a key role in PDE4B binding and any alterations could interfere with the binding. Tetrahydropyran side chain and heterocyclic rings are also suggested to be helpful in PDE4B binding.

    Matched MeSH terms: Crystallography, X-Ray
  10. Gelatine enhances drug dispersion in alginate bilayer film via the formation of crystalline microaggregates
    Thu HE, Ng SF
    Int J Pharm, 2013 Sep 15;454(1):99-106.
    PMID: 23856162 DOI: 10.1016/j.ijpharm.2013.06.082
    In our previous study, a novel alginate-based bilayer film for slow-release wound dressings was successfully developed. We found that alginate alone yielded poor films; however, the addition of gelatine had significantly enhanced the drug dispersion as well as the physical properties. Here, an investigation of the drug-polymer interactions in the bilayer films was carried out. Drug content uniformity test and microscopy observation revealed that the addition of gelatine generated bilayer films with a homogenous drug distribution within the matrix. The FTIR and XRD data showed an increase in film crystallinity which might infer the presence of drug-polymer crystalline microaggregates in the films. DSC confirmed the drug-polymer interaction and indicated that the gelatine has no effect on the thermal behaviour of the microaggregates, suggesting the compatibility of the drug and excipients in the bilayer films. In conclusion, the addition of gelatine can promote homogenous dispersion of hydrophobic drugs in alginate films possibly through the formation of crystalline microaggregates.
    Matched MeSH terms: Crystallography, X-Ray
  11. Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum
    Ahmad H, Ahmad S, Shah SAA, Latif A, Ali M, Khan FA, et al.
    Bioorg Med Chem, 2017 07 01;25(13):3368-3376.
    PMID: 28457693 DOI: 10.1016/j.bmc.2017.04.022
    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.
    Matched MeSH terms: Crystallography, X-Ray
  12. Fulltext Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies
    Kwong HC, Chidan Kumar CS, Mah SH, Chia TS, Quah CK, Loh ZH, et al.
    PLoS One, 2017;12(2):e0170117.
    PMID: 28241010 DOI: 10.1371/journal.pone.0170117
    Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.
    Matched MeSH terms: Crystallography, X-Ray
  13. Studies on the interaction of mononuclear metal(II) complexes of amino‑naphthoquinone with bio-macromolecules
    Kosiha A, Lo KM, Parthiban C, Elango KP
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:778-787.
    PMID: 30423764 DOI: 10.1016/j.msec.2018.10.021
    Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {L = 2‑chloro‑3‑((3‑dimethylamino)propylamino)naphthalene‑1,4‑dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104 M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22 × 105 M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22 μM, respectively.
    Matched MeSH terms: Crystallography, X-Ray
  14. Fulltext Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly
    Antonova SV, Haffke M, Corradini E, Mikuciunas M, Low TY, Signor L, et al.
    Nat Struct Mol Biol, 2018 12;25(12):1119-1127.
    PMID: 30510221 DOI: 10.1038/s41594-018-0156-z
    TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and functional assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex. We discover a key checkpoint function for the chaperonin CCT, which specifically associates with nascent TAF5 for subsequent handover to TAF6-TAF9 and ultimate holo-TFIID formation. Our findings illustrate at the molecular level how multisubunit complexes are generated within the cell via mechanisms that involve checkpoint decisions facilitated by a chaperone.
    Matched MeSH terms: Crystallography, X-Ray
  15. A stable hydrocortisone nanosuspension for improved dissolution: Preparation, characterization and in vitro evaluation
    Ali HS, Khan S, York P, Shah SM, Khan J, Hussain Z, et al.
    Pak J Pharm Sci, 2017 Sep;30(5):1635-1643.
    PMID: 29084684
    Drug nanosuspensions have gained tremendous attraction as a platform in drug delivery. In the present work, a nanosuspension was prepared by a wet milling approach in order to increase saturation solubility and dissolution of the water insoluble drug, hydrocortisone. Size of the generated particeles was 290 nm ± 9 nm having a zeta potential of -1.9 mV ± 0.6 mV. Nanosized particles were found to have a rod shape with a narrow particle size distribution (PDI =0.17). Results of differential scanning calorimetry and X-ray diffraction analyses revealed minor modifications of crystallinity of hydrocortisone following the milling process. Solubility of hydrocortisone was enhanced by nanonization to 875µg/ml ±2.5, an almost 2.9-fold compared to the raw hydrocortisone. Moreover, the nanosuspension formulation substabtially enhanced the dissolution rate of hydrocortisone where >97% of the hydrocortisone was dissolved within 10 minutes opposed to 22.3% for the raw 50% for the raw hydrocortisone and the commercial tablet, respectively. The bioavailability study resulted in AUC 0-9h for HC nanosuspensions (31.50±2.50), which is significantly (p<0.05) higher compared to the AUC 0-9h (14.85±3.25) resulted for HC solution. The nanosuspension was physically stable at room temperature for 24 months.
    Matched MeSH terms: Crystallography, X-Ray
  16. Fulltext The structure of a major surface antigen SAG19 from Eimeria tenella unifies the Eimeria SAG family
    Ramly NZ, Dix SR, Ruzheinikov SN, Sedelnikova SE, Baker PJ, Chow YP, et al.
    Commun Biol, 2021 03 19;4(1):376.
    PMID: 33742128 DOI: 10.1038/s42003-021-01904-w
    In infections by apicomplexan parasites including Plasmodium, Toxoplasma gondii, and Eimeria, host interactions are mediated by proteins including families of membrane-anchored cysteine-rich surface antigens (SAGs) and SAG-related sequences (SRS). Eimeria tenella causes caecal coccidiosis in chickens and has a SAG family with over 80 members making up 1% of the proteome. We have solved the structure of a representative E. tenella SAG, EtSAG19, revealing that, despite a low level of sequence similarity, the entire Eimeria SAG family is unified by its three-layer αβα fold which is related to that of the CAP superfamily. Furthermore, sequence comparisons show that the Eimeria SAG fold is conserved in surface antigens of the human coccidial parasite Cyclospora cayetanensis but this fold is unrelated to that of the SAGs/SRS proteins expressed in other apicomplexans including Plasmodium species and the cyst-forming coccidia Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti. However, despite having very different structures, Consurf analysis showed that Eimeria SAG and Toxoplasma SRS families each exhibit marked hotspots of sequence hypervariability that map to their surfaces distal to the membrane anchor. This suggests that the primary and convergent purpose of the different structures is to provide a platform onto which sequence variability can be imposed.
    Matched MeSH terms: Crystallography, X-Ray
  17. Fulltext Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities
    Kumar CS, Then LY, Chia TS, Chandraju S, Win YF, Sulaiman SF, et al.
    Molecules, 2015 Sep 11;20(9):16566-81.
    PMID: 26378514 DOI: 10.3390/molecules200916566
    A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C₈H₅O(C=O)CH₂O(C=O)C₆H₄X, X = H, Cl, CH₃, OCH₃ or NO₂, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.
    Matched MeSH terms: Crystallography, X-Ray
  18. Aspidofractinine and Eburnane Alkaloids from a North Borneo Kopsia. Ring-Contracted, Additional Ring-Fused, and Paucidactine-Type Aspidofractinine Alkaloids from K. pauciflora
    Yap WS, Gan CY, Sim KS, Lim SH, Low YY, Kam TS
    J Nat Prod, 2016 Jan 22;79(1):230-9.
    PMID: 26717050 DOI: 10.1021/acs.jnatprod.5b00992
    Eleven new indole alkaloids (1-11) comprising seven aspidofractinine and four eburnane alkaloids, were isolated from the stem-bark extract of Kopsia pauciflora occurring in Malaysian Borneo. The aspidofractinine alkaloids include a ring-contracted, an additional ring-fused, a paucidactine regioisomer, two paucidactine, and one kopsine alkaloid. The structures of several of these alkaloids were also confirmed by X-ray diffraction analyses. The bisindole alkaloids isolated, norpleiomutine and kopsoffinol, showed in vitro growth inhibitory activity against human PC-3, HCT-116, MCF-7, and A549 cells and moderate effects in reversing multidrug-resistance in vincristine-resistant human KB cells.
    Matched MeSH terms: Crystallography, X-Ray
  19. Cytotoxic vobasine, tacaman, and corynanthe-tryptamine bisindole alkaloids from Tabernaemontana and structure revision of tronoharine
    Sim DS, Chong KW, Nge CE, Low YY, Sim KS, Kam TS
    J Nat Prod, 2014 Nov 26;77(11):2504-12.
    PMID: 25333996 DOI: 10.1021/np500589u
    Seven new indole alkaloids (1-7) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan Tabernaemontana. Two of the new vobasine alkaloids (1, 3), as well as 16-epivobasine (15) and 16-epivobasenal (17), showed appreciable cytotoxicity toward KB cells (IC50 ca. 5 μg/mL). The structure of the known Tabernaemontana alkaloid tronoharine (8) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis.
    Matched MeSH terms: Crystallography, X-Ray
  20. Crystal Structures and Cytotoxicity of Ortho-Xylene Linked Bis-benzimidazolium Salts
    Iqbal MA, Haque RA, Ahamed SA, Jafari SF, Khadeer Ahamed MB, Abdul Majid AM
    Med Chem, 2015;11(5):473-81.
    PMID: 25553509
    Azolium (imidazolium and benzimidazolium) salts are known as stable precursors for the synthesis of Metal-N-Heterocyclic Carbene (M-NHC) complexes. Recently, some reports have been compiled indicating that benzimidazolium salts have anticarcinogenic properties. The current research is the further investigation of this phenomenon. Three ortho-xylene linked bis-benzimidazolium salts (1-3) with octyl, nonyl and decyl terminal chain lengths have been synthesized. Each of the compounds was characterized using FT-IR and NMR spectroscopic techniques. The molecular geometries of two of the salts (1-2) have been established using X-ray crystallographic technique. The compounds were tested for their cytotoxic properties against three cancerous cell lines namely, human colon cancer (HCT 116), human colorectal adenocarcinoma (HT- 29) and human breast adenocarcinoma (MCF-7). Mouse embryonic fibroblast (3T3-L1) was used as the model cell line of normal cells. The compounds showed selective anti-proliferative activities against the colorectal carcinoma cells. For HCT 116 and HT-29 cells, the IC50 values ranged 0.9-2.6 µM and 4.0-10.0 µM, respectively. The salts 1 and 3 displayed moderate cytotoxicity against the breast cancer (MCF-7) cells with IC50 58.2 and 13.3 µM, respectively. However, the salt 2 produced strong cytotoxicity against MCF-7 cells with IC50 4.4 µM. Interestingly, the compounds demonstrated poor cytotoxic effects towards the normal cells (3T3-L1) as the IC50 was found to be as high as 48.0 µM. Salts 2 and 3 demonstrated more pronounced anti-proliferative effect than the standard drugs used (5-Flourouracil and Tamoxifen).
    Matched MeSH terms: Crystallography, X-Ray
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